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.   ;      1  I  I  ' 


Hunter   Street,    Brunswick   Square,  W.C. 













J.  L.  W.  THUDLCHUM,  M.D. 



'  1884. 

■  t 







Digitized  by  the  Internet  Archive 
in  2015 


A  CENTURY  has  nearly  elapsed  since  the  brain  was  for  the  first 
time  made  the  object  of  physiological  research,  with  the  aid  of 
the  then  newly  discovered  science  of  chemistry.  But  the  attempt 
remained  isolated  at  the  time,  and  was  renewed  only  at  long 
intervals,  mostly  by  inquirers  who  had  no  cohesion  and  little 
sympathy  with  each  other,  and  particularly  had  no  paramount 
object  in  the  prosecution  of  such  an  inquiry.  Now  and  then  an 
eminent  chemist  just  touched  the  problem,  to  leave  it  soon  after 
he  had  recognised  its  inherent  difficulties.  During  the  last  twenty 
years  only  were  more  frequent  attempts  made  to  approach  the 
knowledge  of  the  chemistry  of  the  brain ;  but  these  results  were 
so  little  satisfactory,  that  inquirers  could  not  even  think  of  pro- 
ceeding to  quantitative  investigation  of  normal  relations,  much 
less  of  studying  pathological  phenomena.  It  was  under  such  un- 
promising conditions  that  I  undertook,  about  twelve  j^ears  ago, 
to  make  some  researches  on  this  subject  for  the  then  Medical 
Department  of  the  Privy  Council.  The  j)rogress  which  I  was 
able  to  report  in  1874  was  sufficiently  great  to  ensure  acquiescence 
in  the  continuance  of  my  efforts  on  the  part  of  the  former  authority 
and  subsequently  of  the  Local  Government  Board,  to  whom  the 
functions  with  regard  to  the  administration  of  the  Parliamentary 
grant  for  researches  in  aid  of  pathology  and  medicine,  previously 
exercised  by  the  Privy  Council,  were  transferred.  It  soon  became 
evident  that  the  physiological  inquiries,  which  had  been  intended 
as  an  introduction  to  pathological  ones,  would  occupy  far  more 
time  than  had  been  anticipated.  However,  as  the  information 
grew,  as  the  discoveries  multiplied  in  number  and  gained  in  pre- 
cision, no  hesitation  could  be  felt  in  following  up  the  researches 
to  a  decided  issue.    Thus  I  came  to  trace  the  foundations  of  the 



chemical  constitution  of  the  brain,  the  outlines  of  which  I  have 
the  honour  of  laying  before  the  medical  profession  and  the  general 
scientific  public  in  the  shape  of  the  present  treatise.  The  work 
is  a  systematic  consolidation  of  all  the  researches  on  the  subject 
which  have  been  laid  before  Parliament  in  the  Annual  Eeports  of 
the  Medical  Officer  of  the  Privy  Council  and  Local  Government 
Board  respectively.  The  matter  of  the  work  is  therefore  public 
property,  and  under  these  circumstances  I  think  it  my  duty  to 
specially  avow  my  responsibility  for  its  contents. 

I  should  not  be  surprised  if  some  readers  were,  at  the  first 
glance,  to  think  the  subject  recondite  and  its  treatment  heavy. 
Descriptions  of  complicated  chemical  processes  are  necessarily 
tedious  to  those  who  have  no  practical  concern  in  their  repetition 
or  even  knowledge.  By  some  they  will  j^robably  be  treated  with 
the  consideration  which  Hellenic  literature  received  before  the 
Eenaissance,  and  which  has  been  recorded  in  the  sentence :  '  Grseca 
sunt,  non  leguntur.'  But  I  would  beg  all  readers  to  take  into 
patient  consideration  that  I  had  to  write  a  highly  technical  work 
on  a  most  difficult  subject,  and  to  endeavour  to  make  it  accept- 
able, in  such  a  form  as  it  practically  could  have,  to  anatomists, 
physiologists,  and  ^pathologists,  as  well  as  to  that  principal  part  of 
the  medical  public  which  is  engaged,  like  myself,  in  the  practical 
pursuit  of  the  profession. 

However,  to  all  readers  who  will  enter  upon  the  consideration 
of  the  subject  with  the  intention  of  adding  it  to  their  previous 
stock  of  knowledge,  I  can  promise  the  enjoyment  of  some  intel- 
lectual pleasure.  They  will  find  the  brain  to  be  the  most  diver- 
sified chemical  laboratory  of  the  animal  economy;  they  will  find 
such  numbers  and  varieties  of  hitherto  unknown  and  most  remark- 
able chemical  principles  taking  part  in  such  complicated  chemical 
structures  and  processes,  that  the  explanation  of  the  mental 
phenomena,  and  of  their  aberrations  under  the  influence  of 
disease,  seems  much  less  difficult  than  it  appeared  before  these 

I  have  not  in  this  treatise  entered  upon  any  pathological  con- 
siderations, although  I  have  in  several  smaller  publications  shown 
the  bearings  which  some  of  my  discoveries  have  upon  the  practical 
study  and  treatment  of  diseases.  Thus  I  have  shown  the  morbid 
alteration  of  the  nerve-marrow  in  locomotor  ataxia,  and  the 
occurrence  of  a  kind  of  glycohfemia  to  be  intimately  connected 



with  patholytic  changes  in  substances  of  the  group  of  cerebrosides. 
I  could  go  further  and  unfold,  e.g.,  a  chemical  connection  between 
the  function  of  the  liver  and  that  of  the  brain,  opening  views  into 
the  pathology  of  the  future  and  illuminating,  though  only  with 
the  disappointing  brevity  of  an  electric  spark,  regions  as  dark  as 
those  of  general  paralysis  and  melancholy.  But  I  have  (in  early 
stages  of  my  work)  formed  the  resolution  never  to  propound  a 
generalisation  on  any  subject  before  having  proved  the  validity 
of  all  data  obtainable  by  observation  or  experiment.  And  I  must 
say  that  I  have  not  yet  found  any  subject  in  chemical  biology 
on  which,  governed  by  that  resolution,  I  should  have  liked  to 
proceed  to  generalisation. 

The  principal  reason  for  this  abstention  is  the  circumstance  that 
the  data  or  so-called  facts  available  in  chemical  biology  are  as  yet 
too  incomplete,  and  therefore  unsuitable  for  connected  treatment 
except  with  the  aid  of  hypotheses.  This  circumstance  also  affects 
the  present  treatise,  and  I  have  taken  care  to  point  out  to  the 
reader  cases  where  my  information  was  partial,  or  where  no  data 
at  all  were  as  yet  available.  In  order,  however,  that  the  reader 
may  not,  from  this  avowal,  come  to  an  erroneous  conclusion 
regarding  my  own  estimate  of  the  value  of  the  researches  com- 
municated in  this  treatise,  I  undertake  to  assure  him  that  they 
are  of  fundamental  importance,  and  that  all  further  developments 
in  chemical  neurology  must  start  from  them  as  a  basis.  I  say  this 
in  view  of  the  records  of  the  work  of  all  those  who  have  grappled 
with  the  problem  before  me,  and  in  kindness  to  all  who  may  like 
to  deal  with  it  hereafter. 

The  literary  discussions  on  subjects  of  brain  chemistry  which 
have  taken  place  during  the  last  few  years,  and  in  which  I  was 
obliged  to  take  an  active  part,  have  had  such  an  issue  that  I  was 
happily  enabled  to  exclude  all  controversy  from  the  pages  of  my 
treatise.  I  have  moreover  endeavoured  throughout  to  confine 
my  matter  to  the  narrowest  space  compatible  with  clearness  of 
description  and  accuracy  of  demonstration,  and  it  is  owing  to  this 
resolution  that  I  have  omitted  not  only  references  to  historical 
literature,  but  multifarious  details  of  analytical  figures,  the  repro- 
duction of  which  would  have  enlarged  the  size  and  enhanced  the 
price  of  the  work  without  any  corresponding  advantage  to  the 
greater  number  of  readers.  Those,  however,  who  value  such 
matters  will  find  a  complete  history  of  research  in  brain  chemistry 



detriment  of  the  science  of  which,  even  by  a  short  connection, 
their  names  have  become  permanent  ornaments. 

I  am  in  hopes  that  several  of  the  discoveries  made  on  the  brain, 
and  communicated  in  this  treatise,  will  be  able  to  shed  some  light 
upon  other  subjects  in  biological  chemistry,  which  are  at  present 
little  understood.  I  have  indicated  some  of  my  ideas  on  that 
subject  in  a  few  pages  appended  to  the  division  on  cerebral 
phosphatides,  which  give  a  short,  comparative  consideration  of 
other  phosphatides  of  the  animal  body. 

Phosphatides  are  the  centre,  life,  and  chemical  soul  of  all 
bioplasm  whatsoever,  that  of  j^hants  as  well  as  animals.  Their 
chemical  stability  is  greatly  due  to  the  fact  that  their  fundamental 
radicle  is  a  mineral  acid  of  strong  and  manifold  dynamicities. 
Their  varied  functions  are  the  result  of  the  collusion  of  radicles 
of  strongly  contrasting  properties.  Their  physical  properties  are, 
viewed  from  a  teleological  point  of  standing,  eminently  adapted 
to  their  functions.  Amongst  these  properties  none  are  more 
deserving  of  further  inquiry  than  those  which  may  be  described 
as  their  power  of  colloidation.  AYithout  this  power  no  brain  as 
an  organ  would  be  possible,  as  indeed  the  existence  of  all  bioplasm 
is  dependent  on  the  colloid  state. 

I  was  preaching  in  the  desert  when,  in  1866,  I  advanced  the 
hypothesis,  based  upon  numerous  and  deep  investigations,  that 
the  fall  of  temperature  in  the  collapse-stage  of  cholera,  far  below 
the  normal,  is  due  to  the  destruction  of  the  colloid  state  in 
myoplasm,  produced  by  the  direct  influence  of  the  disease-cause. 
Now,  in  1884,  we  can  demonstrate  to  the  eyes  that  there  are 
bacteria  or  microzymes  which  have  the  power  of  liquifying 
colloids,  while  there  are  others  which  have  not  got  that  power. 
That  the  phosphatides  may  be  capable  of  being  affected  by  the 
former  is  very  probable,  particularly  when  it  is  observed  how  in 
cells  bacteria  congregate  and  multiply  in  close  proximity  to  the 
nuclei.  Now  so-called  softening  of  the  brain  consists  in  the  first 
place  merely  in  the  loss  of  the  colloid  state  on  the  part  of  a  smaller 
or  larger  portion  of  nerve-marrow.  The  bacilli  of  tubercle  may 
effect  such  a  softening ;  but  others  may  have  the  same  power. 
The  next  stage  after  the  fluidification  is  patholysis,  the  splitting 
up  of  the  liberated  immediate  principles  into  their  proximate 
nuclei,  the  same  as  those  which  we  obtain  by  chemolysis.  The 
two  processes,  the  one  in  cholera,  and  the  other  in  softening  of 



the  brain,  illustrate  the  acute  and  chronic  form  of  loss  of  colloida- 
tion  and  of  patholysis  under  the  influence  of  microzymes. 

Some  phosphatides  of  the  brain  probably  permeate  the  neuro- 
plasm in  a  non-colloid  dissolved  liquid  state,  e.g.^  amidomyelin  ; 
and  this  body  has  the  remarkable  property  that  while  perfectly 
soluble  in  water,  and  non-colloid  at  the  ordinary  temperature  and 
at  temperatures  approaching  that  of  the  animal  body,  it  becomes 
colloid  at  temperatures  between  the  normal  and  the  highest  fever 
heat.  It  is  not  impossible  that  some  such  change  may  be  the 
cause  of  death  in  many  febrile  conditions,  and  in  many  cases  of 
death  from  exposure  to  excessive  heat,  in  which  no  adequate 
mechanical  lesion  can  be  discovered. 

A  few  further  examples  may  suffice  to  indicate  some  of  the 
lines  on  which  the  practical  consideration  of  diseases  of  the  brain 
by  the  aid  of  its  chemistry  will,  at  least  in  the  first  instance,  have 
to  proceed.  Many  kinds  of  headache  are  probably  due  to  intra- 
cranially  brewed  chemical  poisons,  or  to  poisons  carried  from  the 
body  to  the  brain  by  the  blood,  whether  fermented  in  the  body, 
or  like  alcohol,  morphia,  and  fusel  oil,  formed  out  of  the  body. 
From  such  occasionally  produced  effects  to  the  constant  produc- 
tion of  similar  effects  by  a  continued  zymosis,  be  it  now  caused 
by  organised  or  unorganised  ferments,  is  not  a  great  step.  Many 
forms  of  insanity  are  unquestionably  the  external  manifestations 
of  the  effects  upon  the  brain-substance  of  poisons  fermented  within 
the  body,  just  as.  the  mental  aberrations  accompanying  chronic 
alcoholic  intoxication  are  the  accumulated  effects  of  a  relatively 
simple  poison  fermented  out  of  the  body.  These  poisons  we 
shall,  I  have  no  doubt,  be  able  to  isolate  after  we  know  the 
normal  chemistry  to  its  uttermost  detail.  And  then  will  come  in 
their  turn  the  crowning  discoveries  to  which  all  our  efforts  must 
ultimately  be  directed,  namety,  the  discoveries  of  the  antidotes  to 
the  poisons,  and  to  the  fermenting  causes  and  processes  which 
produce  them. 


11,  Pembroke  Gardens,  W., 
February,  1884. 




General  view  of  the  subject  matter .  ,  .  .  .1 




Preparation  and  comminution  of  braintissue  .  .  .28 

Extraction  of  brainpulp  and  separation  of  albuminous  or  insoluble 
matter,  white  matter,  buttery  matter,  last  oily  matter,  and 
ultimate  watery  mother-liquor     .  .  .  .  .29 

Process  for  separating  white  matter  into  its  constituents    .  .32 

Treatment  of  the  buttery  matter    .  .  -        .  .  .34 

Treatment  of  the  last  oily  matter  .  .  .  .  .35 

Summary  of  immediate  principles  in  the  crude  state  or  mixtures 
thereof  isolated    .  .  .  .  .  .  .35 

Summary  and  arrangement  in  groups  of  immediate  principles       .  36 


General  properties  of  the  phosphorised  principles   .  .  .39 

Deposition  of  impurities      .  .  .  .  .  .40 

Filtration  of  the  watery  solutions  of  the  phosphorised  matters       .  41 
Solubility  of  phosphorised  matters  in  ether  and  alcohol      .  .42 
A.  Subgroup  of  Mononitrogenised  Monophosphatides.  N  :  P  =  1  : 1  .  42 
1.  Lecithins     .  .  .  .  .  .  .  .42 

Definition    .  .  .  .  .  .  .  .42 

Isolation     .  .  .  .  .  .  .  .  43 

Episode  concerning  the  shifting  of  cadmium  chloride  in  mixtures  of 
lecithin,  parainyelin,  and  amidomyelin  during  recrystallisation 
from  spirit  .  .  .  .  .  .  .44 

Continuation  of  the  description  of  the  process    •    .  .  .45 

Separation  of  lecithin  from  amidomyelin  and  paramyelin  when  all 
are  in  the  free  state        .  .  .  .  .  .45 

Properties  and  compounds  of  lecithin         .  .  .  .46 




Lecithin  cadmium  chloride .          .           .          .           .  .48 

Chemolysis  of  lecithin        .           .           .           .           .  .49 

Note  on  oleic  acid  and  its  reaction  with  oil  of  vitriol  and  sugar     .  51 

Theory  of  lecithins  considered  as  phosphatides       .          .  .52 

2.  Kephalins    .          .           .           .           .           .           .  .52 

a.  Kephalin            .           .          .           .           .           .  .52 

Purification         .           .           .           .           .           .  .52 

Expulsion  of  hydrochloric  acid  from  kephalin  by  water  .  .  53 

Bases  and  salts  which  are  in  combination  with  kephalin  after 

filtration  of  its  aqueous  solution          .           .           .  .54 

Dialysis  of  kephalin        ,           .           .           .           .  .55 

Clarification  and  decolorisation  of  watery  and  ethereal  solutions 

of  kephalin      .           .           .           .           .           .  .55 

Influence  of  animal  charcoal  on  water  solution  of  kephalin  .  56 

Bearing  of  kephalin  in  ether  with  charcoal         .           .  ,56 

Ultimate  analysis  of  kephalin     .           .           .           .  .57 

Solubilities  of  kephalin    .          .          .           .           .  .58 

Reactions  of  the  aqueous  solution  of  kephalin     .           .  .59 

Compounds  of  kephalin  .           ,          .           .           .  .61 

Kephalin  cadmium  chloride        .           .           .           .  .61 

Kephalin  with  hydrochloric  acid  and  platinic  chloride    .  .  62 

h.  Amidokephalin    .          .           .           .          .           .  .64 

c.  Oxikephalin  with  cadmium  chloride        .           .           .  .64 

Behaviour  of  a  similar  salt  with  water    .           .           .  .66 

(1.  Peroxikephalin    .           .           .           .           .           .  .66 

Transformation  of  this  body  into  lead  salt         .           .  .66 
Comparison  of  the  organic  matter  in  the  lead  salt,  with  the  com- 
position of  the  free  body  and  of  the  organic  matter  in  a  salt  of 

kephaloidin  with  cadmium  chloride    .           .          .  .67 

€.  Kephaloidin        .           .           .          .           .           .  .67 

Definition           .           .           .           .           .           .  .67 

Solubility  in  water  and  filtration.           .           .           .  .68 

Bearing  in  dialysing  apparatus  ;  first  and  second  experiments  .  68 

Bearing  of  the  ether  solution  with  water            ,           .  .68 

Reactions  of  the  watery  solution  of  kephaloidin  .           .  .69 

Kephaloidin  lead.           .           .           .           .           .  .69 

f.  Oxikephaloidin  with  cadmium  chloride  .          .           .  .70 

Comparison  of  the  composition  of  the  organic  matter  with  other 

kephalins         .           .          .           .          .          .  .71 

(f.  Decompositions  of  kephalin         .           .           .           .  .71 

li.  Chemolyses  of  kephalins             .           .           .          .  .72 

a.  Limited  chemolysis  by  caustic  soda    .           .           .  .72 

Reactions  of  the  soapy  solution          .           .           .  .73 

Decomposition  of  the  soaps  b}^  hydrochloric  acid  ...  .73 

The  precipitated  fatty  acids    .          ,          .    .       .  .73 

The  acids  soluble  in  alcohol — kephalophosphoric,  kephalic, 

and  a  third  acid      .           .          .          .           .  .73 

Kephalophosphate  of  lead       .           .          .          .  .73 

Kephalic  and  stearic  acid,  and  their  barium  salts      .  .  74 

Glycerophosphoric  acid          .           .           .           .  .76 

Neurin  and  second  oily  base   .           .           .           .  .76 

Summary  of  results  of  limited  chemolysis  of  kephalin  .  76 

|3.  Complete  chemolysis  of  kephalin  by  caustic  soda       .  .77 



Treatment  of  the  filtrate  containing  glycerophosphoric  acid 

and  ammonium  base 
The  glycerophosphate  of  lead  . 
Acid  glycerophosphate  of  calcium 
The  platinic  chloride  precipitate 
y.  First  chemolysis  of  kephalin  with  barita  hydrate 
^  Second  chemolysis  of  kephalin  by  barita 
6.  Third  chemolysis  of  kephalin  by  barita 
Z,.  Fourth  chemolysis  of  kephalin  by  barita 
r/.  Fatty  acids  produced  in  the  chemolysis  of  kephalin  from 
barium  salt  insoluble  in  ether 
The  lead  salt  insoluble  in  ether  :  first,  second,  and  third 

Lead  salt  soluble  in  ether 
Barium  salt  soluble  in  ether,  kephalate  :  product  of  the  first 
chemolysis  . 

9.  Product  of  the  secondary  chemolysis  with  barita  and  caustic 

soda  in  succession  .... 
K.  Theory  of  the  chemical  constitution  of  the  kephalins 

0.  Parami/flin  :  its  isolation,  analysis,  and  compounds 
Preparation  of  free  paramyelin  from  the  cadmium  chloride 

pound  ...... 

Paramyelin  cadmium  chloride  (ox)  . 
4.  Myelin  :  its  isolation,  analysis,  and  cowpounds 
General  definition  of  myelin 

Modes  of  obtaining  myelin  .... 
Differences  and  separation  from  other  cerebral  principles 
Myelin  lead  ..... 
Decomposition  of  lead  salt  by  hydrothion  . 
Subgroup  of  Dinitrogenised  Monophosphatides.  .  N  :  P  =  2  : 1 

1.  Amidomycdin  :  its  isolation,  analysis,  and  compounds 
Process  for  the  isolation  of  amidomyelin 
Amidomyelin  dicadm^um  chloride  compound,  insoluble  in  boiling 

benzol  from  ox  buttery  after  lead  process 
Preparation  of  free  amidomyelin  from  the  cadmium  chloride 
pound  .... 
{a)  By  the  hydrothion  process 

(b)  By  dialysis 

(c)  From  the  acid  mother-liquors 
Properties  of  amidomyelin  . 
Theory  of  amidomyelin  (ox)  as  deduced  from  its  cadmium  chloride 

compound,  and  comparison  with  the  theory  of  sphingomyelin 
(apomyelin)  ....... 

Diagnosis  gind  separation  of  amidomyelin  from  sphingomyelin 

2.  AmidokepMdin :  its  isolcdion,  analysis,  and  comj)Ounds 
Amidokephalin-  ....... 

Transformation  of  this  preparation  into  lead  salt  . 

3.  Sphingomyelin,  type  of  the  diamidated  phosphcUides,  ivhich  con- 

tain no  glycerol:  its  isolcUion,  analysis,  chemolysis,  and  com- 
IJonnds  ........ 

Process  of  separating  apparently  homogeneous  crystallised  bodies 
from  the  alcohol  used  for  the  separation  of  the  cerebrosides  ; 
which  bodies  will  be  shown  to  be  mixtures  by  reagents  . 








Properties  of  the  product    .  .  .  .  .  .107 

Preliminary  elementary  analyses    .....  107 

Comparison  with  this  rosette  or  lycopodium-like  body  of  a  similar 
body  obtained  from  the  cerebrin  mixture  by  ether,  together  with 
the  kephalin,  etc.  .  .  .  .  .  -        .  107 

Chemical  and  physical  properties    .  .  .  .  .108 

Analyses     ........  108 

Isolation  of  sphingomyelin  by  cadmium  chloride  process    .  .  108 

Gradual  purification  of  the  cadmium  chloride  salt  of  sphingomyelin 
by  recrystallisation  from  boiling  spirit  and  extraction  with  boil- 
ing ether  ........  109 

Further  purification  of  the  compound  by  ether,  and  by  recrystal- 
lisation   ........  Ill 

Elementary  analyses  of  cadmium  chloride  salt       .  .  .  Ill 

Preparation  of  pure  sphingomyelin  from  its  cadmium  chloride 
compound  .  .  .  .  .  .  .  112 

Removal  of  the  cadmium  by  diffusion  and  dialysis  .  .112 

Physical  and  chemical  properties  of  sphingomyelin  .  .113 

Elementary  analyses  of  sphingomyelin       .  .  .  .114 

Comparison  of  sphingomyelin  with  apomyelin  from  human  brain  .  114 
Chemolyses  of  sphingomyelin,  with  a  view  of  ascertaining  its 

chemical  constitution  :  experiments  1-4  .  ,  .  .115 

Theoretical  results  of  these  chemolyses       .  .  .  .117 

Compounds  of  sphingomyelin         .  .  .  .  .118 

Compounds  of  sphingom^'^elin  with  cadmium  chloride        .  .119 

C.  Subgroup  of  Dinitrogenised  Diphosphatides.    N:  P  =  2  :2  .120 

Assurin  :  its  isolation  and  analysis     .  .  .  .  ,120 

Assurin  hydrochlorate  platinum  chloride     .  .  .  .120 

Synopsis  of  the  results  of  the  first  and  second  series  of  analyses  and 
theory      ........  121 

D.  Subgroup  of  Nitrogenised  Phosphatide-Sulphatides       .  .  122 

Body  from  group  of  cerebrinacides  .  .  .  .  .122 

E.  Subgroup  of  Nonnitrogenised  Monophosphatides  .  .  122 
E.  Comparative    consideration    of  other  Phosphatides   of  the 

Animal  Body     .......  12-> 

Phosphatide  of  the  milk,  lactophosphatide,  casein  .  .  .  12:J 

Phosphatides  of  the  bile,  cholophosphatides  ;  blood,  hematophos- 

phatides   ........  124 

Phosphatides  of  nucleolar  centres  of  growth  (bioiDlasm,  cells,  etc.), 

cytophospliatides  .  .  .  .  .  .  .  12r> 

(4.  Inorganic  Bases  existing  in  the  Brain  in  combination  with 

Phosphatides     .  .  .  .  .  .  .126 

The  precipitate       .  .  .  .  .  .  •12'' 

The  ammoniacal  filtrate      ......  127 

Distribution  of  the  bases  and  phosphoric  acid         .  .  .128 

H.  Special  Study  of  GtLycerophosphoric  Acid  and  its  Salts,  as 

obtained  from  some  Phosphatides  of  the  Braix  .      •    .  128 
Glycerophosphate  of  lead    .  .  .  .  .  .128 

Glycerophosphate  of  calcium  .  .  .  .  ,129 

Acid  glycerophosphate  of  calcium    .  .  .  .  .129 

Glycerophosphate  of  barium  ,  .  .  .  .130 

The  alcuholo-hydrated  barium  glycerophosphate     .  .  .131 






A.  Subgroup  of  the  Cerebrosides        .          .          .          .  .134 

General  properties  of  the  subgroup  .          .           .           .  .134 

1.  Separation  of  the  cei-ehroside  principles  of  the  braiii  ,       .  .136 
Spirit  treatment      .           .           .           .           .           .  .136 

Lead  acetate  treatment       .           .           .           .           .  ,136 

Absolute  alcohol  treatment  without  fractionation  of  precipitate  .  137 

Separation  of  phrenosin  and  kerasin  by  fractional  precipitation  on 

cooling     .           .           .           .           .          .           .  .137 

2.  Phrenosin  and  its  derivates           .           .           .           .     ,  .  138 
a.  Further  purification  of  phrenosin  by  cadmium  chloride,  ether, 

and  hydrothion           ,           .           .           .           .  ,138 

Elementary  analysis  of  phrenosin            .           .           .  .139 

Consideration  of  the  methods  of  analysis           .           .  .139 

h.  Cheraolysis  of  phrenosin  by  sulphuric  acid  in  watery  solution  ,  141 

Introduction        .           .           .           .           .           .  .141 

The  apparatus. — The  leaden  tubes. — The  hot-air  stove   .  .141 

Preliminary  purification  from  inorganic  salts  of  the  phrenosin  to 

be  chemolysed  .           .           .           .           .           .  .142 

Chemolysis  of  the  purified  substance       .           .           .  .142 

The  acid  filtrates .           .           .           ,           .           .  .  142 

c.  Cerebrose,  a  new  crystallised  sugar  .  .  .  .143 
The  crystals. — Cerebrose  .  .  .  .  .  ,143 
Reducing  power  of  cerebrose  over  cupro-potassic  tartrate  .  143 
Polarising  power  of  solution  of  cerebrose  .  .  ,144 
Other  properties  of  cerebrose  .  .  .  .  .144 
The  uncrystallised  cerebrose  .  .  .  .  .145 
Cerebrosic  acid  .  .  .  .  ,  .  .145 
Synopsis  of  analyses  of  barium  cerebrosate  .  .  .146 
Transformation  of  barium  salt  of  cerebrosic  acid  into  zinc  salt  .  147 
Attempt  to  produce  cerebrosic  acid  from  free  cerebrose  .  .147 
Caramel  obtained  in  the  chemolysis  of  phrenosin  in  which  cere- 
brosic acid  was  formed            .           .           .           ,  .147 

d.  Sphingosin,  a  new  alkaloid,  as  sulphate,  and  fatty  acids  .  149 
Removal  of  the  sulphuric  acid  by  caustic  alkali  .      .     .  .149 

Sphingosin  sulphate  and  hydrochlorate    ....  150 

Consideration  of  the  general  chemical  function  of  sphingosin  .  151 

Neutral,  acid,  and  basic  salts  ;  bearing  of  the  sulphate  .  .151 

Bearing  of  the  hydrochlorate       .           .           .           .  .152 

Sphingosin  with  potash    .           .           .           .           .  .152 

Separation  of  psychosin  from  sphingosin  .           .           .  .152 

Fatty  acids  and  matters  soluble  in  ether,  being  products  of  the 

chemolysis  which  yields  sphingosin      .           .           .  .153 

e.  Psychosin,  its  properties  and  metamorphoses     .          .  .154 
Analysis  of  psychosin       .          .           .          .          .  .  154 

Psychosin  sulphate           .           .           .           .           .  .  154 

Psychosin  hydrochlorate  .           .           .           .           .  .155 

Psychosin  and  ammonia  .           .           .           .           .  .155 

Chemolysis  of  psychosin  by  dilute  sulphuric  acid           .  .155 





Purple  reaction  with  oil  of  vitriol  .  ,  .  .156 

Isolation  of  the  purple  products  .  .  .  .  .158 

Caramel  of  psychosin       ,  .  .  .  .  .158 

Tabular  view  of  the  data  concerning  the  caramel  of  psychosin  .  158 
Remarks  on  the  caramels  .  .  .  .  .158 

f.  Intermediate  products  of  the  chemolysis  of  the  cerebrosides  with 

sulphuric  acid  :  hydrated  phrenosin,  sesthesin,  psychosin  .  159 
Crystallised  soluble  in  ether  product. — .-Esthesin  .  .160 

(J.  Chemolysis  of  phrenosin  by  sulphuric  acid  in  alcoholic  solution  ; 

formation  of  ethylic  neurostearate       .  .  .  .162 

The  process         .  .  .  .  .  .  .162 

Neurostearic  ether  ......  162 

Psychosin  sulphate  ......  164 

h.  Action  of  heat  upon  phrenosin  ;  formation  of  a  caramel  .  164 
Preliminary  experiments  .           .           .           .           .  .164 

First  experiment  .  .  .  .  .  .  .165 

Second  experiment  .  .  .  .  .  .166 

Tabular  view  of  the  data  concerning  caramel  of  phrenosin         .  167 

i.  Special  reactions  of  phrenosin     .  .  .  ,  .167 
Reaction  of  phrenosin  with  oil  of  vitriol,  chloroform  and  glacial 

acetic  acid  ;  spectral  phenomena  of  the  product         .  .167 
Reaction  of  phrenosin  with  Pettenkofer's  test ;  and  spectrum  of 
its  product       .......  167 

Ic.  Theory  of  the  chemical  constitution  of  phrenosin  .  .168 

3.  Kerasin,  the  second  cerebroside :  its  isolation  and  properties         .  172 
Introduction  .  .  .  .  .  .  .172 

Mode  of  isolation     .  .  .  .  .  .  .172 

Mode  of  purification  ......  173 

Special  consideration  of  the  properties  of  kerasin  which  are  made 
use  of  for  its  isolation      .  .  .  .  .  .174 

Reactions  of  kerasin  .  .  .  .  .  .175 

Elementary  analyses  and  theory  of  kerasin  .  .  .176 

Chemolysis  of  kerasin         .  .  .  .  .  .177 

Analysis  of  the  sulphate  obtained,  and  comparison  with  the  com- 
position of  psychosin  sulphate  and  sphingosin  sulphate    .  .177 
B.  Subgroup  of  the  Cerebrinacides,  or  Cerebrin  Bodies  which 

COMBINE  WITH  METALLIC  OxiDES  .  .  .  .178 

1.  General  observations  on  the  subr/roup  .  .  .  .178 
Separation  of  these  substances  from  the  cerebrin  mixture  by  lead 

acetate  and  ammonia      .  .  .  .  .  .178 

The  lead  salts         .  .  .  .  .  .  .178 

2.  Cerebrinic  arid  :  if-s  isolfdlon  and  jjvopertir.s  .  .  .  179 
Caramel  of  cerebrinic  acid  :  first  and  second  experiments  .  .179 
Third  and  fourth  experiments  .  .  .  .  .180 
Tabular  view  of  the  data  concerning  the  caramels  of  cerebrinic  acid  .  1 80 

3.  Sulphurised  principles,  spliero-eerehrin,  and  others  .  .  180 
Mode  of  separating  these  substances  from  the  cerebrin  mixture     .  180 
The  crude  lead  compound  (ox-cerebrins)     .           .           .  .181 
(^uantation  of  lead  and  organic  matter  and  of  sulphur  and  phos- 
phorus in  the  dark  lead  salt        .           .          .          .  .181 

Attempt  to  isolate  the  sulphurised  principle  .  .  .181 

Decomposition  of  the  dark  lead  salt  (ox-cerebrins)  by  oxalic  acid 
in  boiling  spirit  ......  182 



Insoluble  lead  salt  (oxalate) 
The  organic  matter  from  the  lead  salt 

4.  Spherocerebrin  ..... 

5,  Principal  and  second  product  from  darh  lead  salt 
The  principal  product  from  dark  lead  salt  (ox-cerebrins) 
Synopsis  of  the  percentages  found  and  the  hypothesis  applied 

C.  SuBrxKoup  OF  Cerebrosulphatides  or  non-albuminous  Immediate 

Principles  Containing  Sulphur  as  an  Essential  Ingredient 
Introduction  ...... 

Human  mixed  cerebrins— barita  process  applied  for  their  separa 


The  process  ..... 
Nature  of  the  precipitate  produced  by  barita 
Matters  soluble  in  cold  benzol 
The  barita-compound  soluble  in  cold  benzol  and  insoluble  in  alcohol 
Synopsis  of  data  ..... 

D.  Subgroup  of  Amidolipotides,  or  Nitrogenised  Fats 

1.  Bregenin :'  its  isolation  and  properties 
Mode  of  isolation  ..... 
Physical  and  chemical  properties  of  bregenin 
Synopsis  of  analyses  and  theory  . 

2.  Krinosin  :  its  isolation  and  j)7'operties 
Mode  of  preparing  krinosin 

Synopsis  of  the  means  of  elementaiy  analyses  and  theory 
formula  .  .  .... 

E.  Subgroup  of  Alkaloids    .  .  .  . 

1.  Alkaloids  from  the  human  brain 

1.  Hypoxanthin  ..... 

2.  Second  alkaloid  .... 
Synopsis  and  computation  of  analyses  . 

3.  Third  alkaloid  ..... 

2.  Alkcdoids  contained  in  ox  brain  . 
Analyses  and  theory  .... 
Computation  of  analyses    ^  .  .  . 

E.  Subgroup  of  Amido- Acids  and  Imides 
1.  Leuciu  and  allied  bodies  ;  tyrosin 

Portion  soluble  in  alcohol  ,  .  .  . 

Portion  insoluble  in  alcohol  .  .  . 

Note  on  a  peculiar  potassium  salt 



A.  Subgroup  of  Alcohols     .  .  ,  ...  .199 

Cholesterin  .  .  .  .  .  .  .199 

Reaction  of  cholesterin  with  oil  of  vitriol  and  chloroform  ;  spectral 
phenomena  of  the  product         .....  200 

Reaction  of  cholesterin  with  oil  of  vitriol  and  glacial  acetic  acid  .  201 



B.  Subgroup  of  Carbohydrates       .  .  ,  .  ,  202 
Inosite          ........  202 

Compounds  of  cerebral  inosite  with  cupric  oxide  .  .  .202 

Compound  of  inosite  from  ox  brain  ....  203 

Compound  of  'inosite  from  human  brain    .  .  .  .201 

C.  Subgroup  of  (Nonnitrogenised)  Organic  Acids  .  ,  .  205 

1.  Lactic  acid  .......  205 

Summary  of  analyses  of  zinc  lactate  from  human  brain    .  .  205 

Summary  of  analyses  of  zinc  lactate  from  ox  brain  .  .  206 

Physical  peculiarities  of  the  lactic  acid  from  brain  and  its  zinc  salt  206 
Peculiarities  of  the  calcium  salt  of  lactic  acid  from  human  brain  .  208 

2.  Formic  acid         .  .  .  .  .  .  .209 

.3.  Succinic  acid        .  .  .  .  .  .  .  209 

(a)  In  ox  brain      .......  209 

[h)  In  the  human  brain     ......  210 



Chemolysis  by  barita  of  neuroplastin  from  brain  .  .  .  212 

Nitrogen  as  ammonia  from  neuroplastin    .  .  .  .215 

Total  of  insoluble  barium  salts  obtained  from  10  g.  neuroplastin  .  215 
Barium  retained  by  amido -alkaloid-acid,  mixture  .  ,  215 

Quantation  of  acetic  acid  and  tyrosin  from  neuroplastin  .  .216 
Leucins  from  100  g.  of  ox-neuroplastin     .  .  ,  .  216 

C^uantation  of  copper  in  the  three  products  .  .  .  216 

Organic  body  from  mercuric  chloride  and  soda  precipitate  .  217 

Properties  of  common  tasteless  leucin  and  of  its  copper  com- 
pound, studied  with  a  view  of  establishing  its  diagnosis  from 
its  isomer  glycoleucin     .  .  .  .  .  .217 

Quantations  of  solubility   .  .  .  .  .  .217 

Stability  and  regularity  of  composition  of  leucin  copper  compound  218 
Leucin  obtained  by  crystallisation  from   amido-mixture  from 
chemolysis  of  neuroplastin        .  .  .  .  .220 

Glycoleucin,  the  first  chemolytic  isomer  of  leucin,  its  properties 
and  combinations  ......  221 

Solubility  of  the  cupric  salt  of  glycoleucin  in  cold  and.  boiling 
water     ........  222 

Elementary  quantation  of  glycoleucin,  prepared  from  insoluble 
copper  salt         .......  222 

Synopsis  of  theory  and  data  .....  22o 

Solubility  in  water  at  18°  .  .  .  .  .  .  223 

A  new  reaction  and  compound  of  cerebral  tyrosin  .  .  223 

Synopsis  of  data  and  theory         .....  224 

New  alkaloids  obtained  from  neuroj^lastin  by  cKemolysisi .  .  225 

Mode  of  isolation  of  alkaloids  from  amido-mixture  .  .  225 

Separation  of  the  alkaloidal  matter  into  two  groups  b}'  absolute 

alcohol   .  .  .  .  .  .  .  .  226 

Elementary  quantation  of  this  new  alkaloid         .  .  .  227 

Separation  of  the  alkaloidal  matter  into  two  groups  by  cupric 
acetate  and  absolute  alcohol      .  .  .  .  .227 

Synopsis  of  results  and  theory      .....  227 





Brain  Ash     ,  .  .  .  .  .  .  .229 

'  YIII. 




FROM  THE  Human  Brain  .....  231 

Synopsis  of  the  results  of  analysis  of  grey  tissue  of  human  brain  .  233 

B.  Quantation  OF  THE  Chemical  Constituents  of  the  White 

Tissue  of  the  Human  Brain  .....  234 

Ether  extract  of  the  cerebrin  deposit       ....  234 

Synopsis  of  the  results  of  analysis  of  white  tissue  of  human  brain  236 

C.  Quantation   of   the  Absolute  and  Specific  Gravities  of  a 

Human  Brain  and  of  Several  Parts  .  .  .  236 

Quantation  of  the  specific  gravity  of  white  tissue  and  grey  tissue 

of  the  human  brain       .  .  .  .  .  .237 

Quantations  of  the  specific  gravities  of  white  and  grey  tissue  from 

different  parts  of  the  brain        .....  238 

D.  Sketch  of  a  Systematic  Quantitative  Analysis  of  the  Brain  .  242 

Analysis  of  the  white  matter        .  .  .  .  .  243 

Treatment  of  the  ether  solution  ;  separation  of  its  ingredients 

from  each  other  ......  243 

Treatment  of  the  insoluble  in  boiling  spirit  part  (of  the  ether 

extract  boiled  with  lead  acetate)  ....  244 

Treatment  of  the  soluble  in  spirit  part      .  .  .  .244 

Separation  of  cholesterin  from  myelin  lead  .  .  .  244 

Solution  in  spirit  of  lecithin,  cerebrol,  yellow  colouring  matter, 

neutral  matter,  and  some  cholesterin    .  .  .  .  245 

Chemolysis  of  the  lecithin,  etc.,  mixture  with  barita       .  .  245 

Products  of  the  barita  chemolysis  of  the  lecithin  mixture  which 

are  insoluble  in  water    ......  245 

Treatment  of  the  alcoholic  solution  which  has  deposited  the  white 

matter   .  .  .  .  .  .  .  .246 

Treatment  of  the  concentrated  alcoholic  solution  which  has  depo- 
sited the  buttery  matter  .  .  ,  .  .  .246 
Analysis  of  the  united  buttery  and  last  oily  matters  .  .  247 
Chemolysis  of  the  last  residue  of  the  buttery  and  last  oily  matter 

which  was  not  precipitated  by  lead  acetate       .  .  .247 

Separation  of  the  ingredients  of  the  buttery  matter  by  a  process 

in  which  caustic  barita  is  employed       .  .  .  .249 

Analysis  of  the  cerebrin  mixture  .....  250 

E.  A  Preliminary  Experiment  for  the  Quantation  of  Consti- 

tuents OF  AN  Entire  Human  Brain    ....  252 

Quantation  of  the  ingredients  of  the  left  hemisphere        .  .  252 

Quantation  of  the  ingredients  of  the  right  hemisphere      .  .  254 

Quantation  of  the  ingredients  of  the  cerebellum   .  .  .  255 

Quantation  of  the  constituents  of  the  mesenkephalon     .  .  .  255 

Table  showing  results  of  the  quantitative  analysis  of  a  human  brain  257 







The  following  work  is  a  contribution  towards  a  system  of  chemical 
statics  of  the  brain,  and  treats  in  the  first  instance  of  brain  matter 
as  a  whole,  without  separating  white  from  grey  rnatter  ;  it  isolates 
and  scrutinises  the  several  chemical  constituents  of  nerve-matter, 
and  endeavours,  by  the  study  and  consideration  of  the  peculiari- 
ties of  each,  and  their  combination,  to  obtain  sufficient  insight 
into  normal  and  abnorm-al  chemical  functions  to  enable  us  in  time 
to  guide  or  to  correct  them. 

It  is  thus  found  that  this  apparently  so  simple  nerve-marrow, 
or  neuroplasm,  is  a  compound  and  mixture  of  a  large  number  of 
heterogeneous  principles  arranged  in  such  a  manner  as  to  vanish 
completely  from  appearance  as  chemical  individuals  ;  the  com- 
pounds so  interpenetrate  each  other  that  the  resulting  material  is 
aj^parently  homogeneous,  during  life  completely  so,  when  seen 
with  high  powers  of  the  microscope,  and  although  in  death  the 
homogeneity  partly  vanishes,  yet  even  the  appearance  of  the 
cylinder  axis  cannot  be  utilised  chemically  at  present,  and  the 
isolation  and  recognition  of  any  ingredients  is  entirely  dependent 
upon  most  circumstantial  chemical  proceedings. 

During  these  proceedings  the  first  striking  fact  which  meets 
the  inquirer  is  that  neuroplasm  contains  abundance  of  water. 
This,  in  conjunction  with  the  peculiar  manner  in  which  the  water 



is  contained,  engenders  a  mobility  of  ultimate  particles  within 
certain  limits  of  movement.  It  also  gives  penetrability  by  liquid 
diffusion,  while  excluding  porosity  and  its  caj)illary  effects  ;  by 
which  means  a  ready  nutrition  by  diffusion  in  one  direction,  and 
ready  cleansing  from  the  effete  crystallisable  products  of  life  in 
another,  are  ensured.  Consequently  the  brain  as  a  whole  is 
essentially  made  up  of  colloid  matter,  and  may  be  compared  to  a 
colloid  septum,  on  the  one  side  of  which  is  arterial  blood  and 
cerebrospinal  fluid  of  the  ventricles,  on  the  other  side,  however, 
is  cerebrospinal  fluid  of  the  arachnoideal  space  and  venous  blood. 
It  follows  from  this  that  the  large  amount  of  water  present  in  the 
brain  is  not  there,  so  to  say,  mechanically  only,  like  water  in  a 
sponge,  and  capable  of  being  pressed  out  mechanically,  but  is 
chemically  combined  as  colloid  hydration  water,  or  better,  water  of 

All  soft  organs  of  the  body  contain  about  three  quarters  of 
their  weight  of  colloidation  water,  fixed  within  the  organised 
limits  of  cells  and  fibres  of  all  kinds.  Cells  and  fibres  are  thus 
apparently  not  very  different  in  respect  of  their  mechanical  con- 
dition from  brain  matter.  Indeed,  the  difference  is  less  in  the 
manner  of  the  condition  than  in  the  agents  by  means  of  which 
the  condition  is  brought  about.  It  is  in  effect  mainly  by  the 
number  and  nature  of  these  agents  that  brain  matter  is  distin- 
guished from  other  colloid  tissues.  It  contains  a  considerable 
amount  of  an  albuminous  l)ase.  Whether  this  is  distributed  in 
the  form  of  sheaths  to  fibres  of  nerve  marrow,  or  whether  it  is 
laid  into  hollow  spaces  between  the  fibres,  and  acts  as  a  cement — 
whether  it  is  mixed  or  combined  chemically  with  the  rest  of  the 
matters  constituting  nerve  marrow — must  be  discussed  later.  It 
may  be  present  in  all  forms,  but  does  not  seem  to  be  present  in  a 
liquid  unattached  form,  as  in  serum.  It  appears  that  the  bearing 
of  soluble  albumen  when  placed  in  presence  of  some  of  the  pecu- 
liar brain  matters  changes  from  that  which  it  ordinarily  observes, 
no  doubt  by  an  influence  of  these  brain  matters  amounting  almost 
to  combination.  The  bearing  of  albumen  in  the  brain  being  thus 
seen  to  be  governed  by  the  matters  peculiar  to  the  brain,  the 
present  researches  have  in  the  first  instance  not  been  directed 
upon  the  condition  and  nature  of  the  albumen  in  the  brain,  but 
upon  the  peculiar  matters  which  seem  not  only  to  govern  the 
albumen,  but  by  their  manifold  chemical  affinities  assist  promi- 



nently  in  producing  its  singular  mechanical  arrangements,  chemical 
function,  and  sensory  and  volitional  action  and  reaction. 

It  is  not  asserted  that  these  matters,  or  any  of  them,  occur  exclu- 
sively in  brain  matter,  but  being  present  in  the  nerves,  they 
consequently  can  be  extracted  from  all  sensitive  or  contractile 
tissues.  They,  or  some  of  them,  also  occur  in  aggregations  of 
loose  cells,  such  as  the  blood-corpuscles  and  pus-corpuscles  ;  others 
are  present  in  serum,  and  others  again  in  secretions,  such  as  bile  ; 
but  the  quantities  in  which  these  bodies  are  met  with  in  parts 
and  matters  other  than  those  of  the  nervous  system  is  very  far 
less  than  that  in  which  they  occur  in  the  nervous  system. 

The  great  quantity  of  these  matters  occurring  in  the  brain 
forms  three  groups  ;  the  members  of  one  contain  at  least  five, 
sometimes  six,  elements,  amongst  which ,  is  phosphorus  ;  hence 
they  may  be  termed  phosphorised  bodies.  The  members  of 
the  second  group  contain  four  elements,  amongst  them  nitrogen, 
but  no  phosphorus,  and  therefore  are  termed  NITROGENISED 
BODIES.  The  members  of  the  third  group  contain  only  three 
elements,  carbon,  hydrogen,  and  oxigen,  present  also  in  the  other 
two  groups,  but  neither  phosphorus  nor  nitrogen,  and  ma}^  be 
termed  oxigenised  bodies. 

The  group  of  the  phosphorised  bodies  contain  the  phosphorus 
in  the  form  of  phosphoric  acid  combined  with  from  two  to  five 
organic  compound  radicles.  As  the.  earliest  known  body  of  this 
group,  kcithin,  yielded  its  phosphoric  acid  mainly  in  combination 
with  glycerol,  as  glycerophosphoric  acid,  it  was  supposed  that  the 
phosphorised  bodies,  of  which  a  number  were  theoretically 
admitted  to  exist,  were  constituted  like  the  fats,  by  combination 
of  compound  organic  radicles  with  the  radicle  of  glycerol,  in  other 
words,  that  they  were  ethers  of  the  alcohol  glycerol,  and  con- 
tained the  phosphoric  acid  as  an  inserted,  and  not  as  a  funda- 
mental radicle.  But  as  we  now  know  at  least  one  phosphorised 
principle  from  the  brain  which  does  not  contain  any  glycerol,  and 
does  therefore  not  yield,  on  chemolysis,  any  glycerophosphoric 
acid,  but  phosphoric  acid  merely  without  any  attached  organic 
radicle,  we  thereby  obtain  a  new  insight  into  the  chemical  consti- 
tution of  the  phosphorised  substances  altogether,  and  are  under 
the  necessity  of  subjecting  their  theory  to  a  revision.  According 
to  the  result  of  this  revision  the  phosphorised  substances  are  not 
glycerides  at  all,  as  commonly  defined,  and  have  nothing  in 




common  with  fats  considered  as  glycerides,  except  that  some  of 
them  contain  certain  fatty  acids  also  present  in  fats,  while  they 
differ  in  physical  and  chemical  properties  widely  from  fats.  In 
accordance  with  this  new  knowledge,  I  have  termed  the  phos- 
phorised  substances  phosphatides,  that  is  to  say,  substances  which 
are  similar  to  (but  not  by  any  means  identical  with)  phosphates, 
on  the  assumption  that  their  basal  or  principal  joining  radicle  is 
that  of  phosphoric  acid,  and  that  in  this  acid  one,  two,  or  three 
molecles  of  hydroxyl  may  be  replaced  by  radicles  of  alcohols, 
acids,  or  bases,  and  that  to  a  molecle  formed  by  three  such  sub- 
stitutions there  may  yet  be  attached,  either  by  substitution  of  an 
element  in  a  radicle  itself  already  substituted  (side-chain),  or  by 
addition  with  elimination  of  water  from  the  added  radicle,  a 
fourth  radicle,  and  that  thus  bodies  of  the  following  typical 
formulse  may  be  produced  : 

Phosphoric  Acid. 

j  HO  (Hydroxyl). 
.  (Phosphoryl)  OP     HO  (Hydroxyl). 

(  HO  (Hydroxyl). 

Nonnitrogenised  Phosphatide. 

Example  :  Kephalophosphoric  acid. 

l'  Kephalyl. 
(Phosphoryl)  OP  Stearyl. 

I  Glyceryl. 

Nitrogenised  Phosphatide. 
Example  :  Lecithin. 

i  Oleyl. 

(Phosphoryl)  OP  Margaryl. 

I  Glyceryl. 


Lin itrogenised  Phosph a t id e. 

Example  :  Amldomyelin. 

i  Acid  radicle. 
(Phosphoryl)  OP     Alcohol  radicle. 

(  Alkaloidal  or  basic  radicle  (substituted). 


Alkaloidal  anhydride  (attached  as  side- 



The  bodies  to  which  the  foregoing  formulae  may  be  applied 
contain  the  phosphorised  radicle  once,  and  may  therefore  be 
termed  monophosphatides ;  but  there  are  present  in  the  brain  and 
other  protoplastic  centres,  bodies  which  contain  the  phosphorised 
radicle  twice,  and  which  may  therefore  be  described  as  diphospha- 
tides  ;  the  immediate  principle  representing  this  subgroup  contains 
about  seven  per  cent,  of  phosphorus,  and  may  perhaps  be  consti- 
tuted according  to  the  following  formula  : 

Dinitrogenised  Dipliosphatide. 

Example  :  Assurln. 

Acid  radicle.         )  |  Acid  radicle. 

Alcohol  radicle.       ■  PO— OP  Alcohol  radicle. 

Alkaloidal  radicle.  )  (  Alkaloidal  radicle. 

I  shall  not  in  this  place  dilate  upon  the  nonnitrogenised  phos- 
phatides, of  which  I  have  given  a  product  as  an  example,  although 
there  are  probably  two  such  immediate  principles  contained  in 
that  part  of  the  spirituous  brain  extract  which  is  conveniently 
termed  the  buttery  matter ;  but  I  shall  at  once  pass  to  a  short 
consideration  of  the  mononitrogenised  monophosphatides,  of 
which  lecithin  is  the  earliest  known,  and  was,  before  the  institu- 
tion of  my  researches,  the  only  one  of  which  any  closer  know- 
ledge existed. 

In  this  subgroup  nitrogen  is  to  phosphorus  in  the  proportion  of 
one  atom  to  one  atom,  a  relation  to  be  expressed  by  the  formula 
N  :  P  1  :  1 .  Of  the  educts  of  the  brain  four  species  with  all  their 
varieties  belong  to  this  subgroup,  namely,  the  lecithins,  kephalins, 
paramyelins,  and  myelins ;  a  product  also  may  be  alluded  to, 
obtained  from  a  dinitrogenised  educt  by  the  loss  of  a  nitrogenised 
radicle,  namely,  splilngomyelic  add.  This  latter  contains  no  glycerol ; 
the  Jecithins,  and  kephalins,  and  paramyelins  probably  contain 
glycerol,  and  yield  glycerophosphoric  acid;  of  the  myelins,  the 
constitution  in  this  particular  respect  has  yet  to  be  ascertained. 

Lecithin,  originally  obtained  from  and  named  after  its  occur- 
rence in  eggs,  is  only  with  difficulty  evolved  from  the  brain,  on 
account  not  only  of  the  many  stages  of  the  processes  necessary 
for  its  isolation,  but  also  on  account  of  its  readiness  to  decompose 
under  certain  conditions.  This  tendency  is  greatest  in  the 
presence  of  hydrochloric  acid  and  platinic  chloride,  with  which 
lecithin  readily  combines.    It  ceases  almost  entirely  when  lecithin 



is  combined  with  cadmium  chloride,  and  the  compound  is  dried. 
In  the  free  state  and  in  concentrated  solutions,  it  has  an  apparently 
spontaneous  tendency  to  change  and  assume  colour,  due  no  doubt 
to  the  known  tenderness  of  the  oleyl  radicle  by  which  it  is 
characterised  ;  but  the  tendency  to  apparently  spontaneous  lysis 
into  proximate  nuclei  is  not  so  great  as  is  supposed  by  most 
authors,  and  can  now  be  almost  entirely  obviated  by  the  improved 
processes  for  its  isolation,  which  I  shall  have  to  describe  below. 
It  is,  however,  the  most  easily  decomposable  member  of  this 
group,  and  this  lability  furnishes  a  valuable  key  to  the  explana- 
tion of  many  changes  in  the  sick  body,  which  may  arise,  or  have 
been  proved  to  arise,  from  its  decomposition.  I  have  not  hitherto 
found  reason  to  suppose  that  there  is  a  dinitrogenised  lecithin 
present  in  the  brain  ;  but  in  view  of  the  dinitrogenised  educts 
which  will  be  described,  the  possibility  of  this  occurrence  must 
not  be  lost  sight  of. 

I  have  given  the  explicit  formulae  of  the  lecithins  considered 
as  phosphatides  under  the  chapter  relating  to  them  ;  the  con- 
tracted formulae  are  : 

Oleo-i^almito-glycero-neuro-phosphatide  =  0^.2^82^^^)^. 

Oleo-margaro-glycero-neuro-phosphatide  =  C43Hg4NPO^. 

Oleo-stearo-glycero-neuro-phosphatide  =  C^^Hg,^.NPOg. 

Of  the  second  lecithin,  there  have  been  analysed  the  following 
salts  : 

Cadmium  chloride  salt 
Hydrochlorate    -       .  - 
Hydrochlorate  platino  chloride 

-  C,3H,,NP0,-{-CdCl,. 

-  2(C,,H,,NP0,  +  HCl)  +  PtCl,. 

In  the  chemolyses  the  oleic,  margaric,  palmitic,  and  stearic  acids 
were  isolated,  oleic  acid  characterising  the  phosphatide ;  stearic 
acid  was  always  present  in  very  small  quantities  only  ;  it  was 
probal.)le  that  of  stearic  acid  the  two  isomers  discovered  in  these 
researches  may  sometimes  be  present  in  lecithins.  Regarding  the 
l  eputed  identity  of  margaric  and  palmitic  acid,  I  still  entertain 
some  doubts,  which  have  been  rather  increased  than  diminished 
by  the  discovery  of  the  isomers  alluded  to.  Besides  these  acids 
the  lecithins  always  yielded  glycerophosphoric  acid  and  neiirin. 
A  specimen  obtained  from  cadmium  chloride  salt  soluble  in  cold 


benzol,  was  recently  analysed  and  found  to  answer  to  the  fore- 
going description. 

As  the  lecithin  species  is  characterised  by  the  presence  of  the 
radicle  of  oleic  acid,  so  the  kephalin  species  is  characterised  by 
the  presence  of  the  radicle  of  a  peculiar  acid,  to  which  I  have 
given  the  name  of  kephalic  acid.  This  acid  is  even  more  changeable 
than  oleic,  and  imparts  its  quality  to  all  the  compounds  in  which 
it  is  present.  The  change  in  these  cases  seems  to  be  either 
acquisitive,  e.g.  by  accession  of  oxigen,  or  intramolecular,  e.g.  by 
transposition  of  atoms,  but  does  not  appear  to  lead  to  lysis  into 
proximate  nuclei  so  easily  as  in  the  case  of  lecithin.  The  second 
fatty  acid  radicle  in  the  case  of  the  principal  kephalin  is  stearyl, 
other  radicles  occurring  only  in  extremely  small  quantities.  The 
members  of  this  subgroup  vary  in  the  amount  of  oxigen  which 
they  exhibit  on  analysis,  in  a  manner  so  as  to  be  apparently  sharply 
characterised  thereby.  But  this  variability  of  the  constituent 
oxigen  may  be  transitional,  and,  on  the  whole,  this  remarkable 
feature,  which  none  of  the  other  phosphatides  exhibit,  requires 
much  further  investigation  before  it  is  adducible  to  any  very 
precise  theory. 

A  kephalin  mav  therefore  be  defined  as  kephalo-stearo-glycero- 
neuro-phosphatide,  and  represented  by  the  formula 

To  be  a  kephalin  a  phosphatide  must  contain  the  radicle 
kephalyl,  or  a  homologue,  which  governs  most  of  the  properties  of 
the  compound ;  its  peculiar  properties  prevail  over  those  of  the 
second  acid. 

A  kephalin  with  palmityl,  Cj^Hg^O^,  in  place  of  stearyl,  would 
have  the  summary  formula,  C^^H^^NPOg  +  aq.  ;  a  kephalin  with 
margaryl,  CjwHggO^  would  be  C^^H-oNPOc,  +  aq.  If  there  were 
several  homologous  kephalic  asids,  such  as  some  analyses  seem  to 
indicate,  then  for  a  kephalyl  of  formula  C^wUgQC.:,,  combined  with 
either  stearyl,  margaryl,  or  palmityl,  the  foregoing  formulae  would 
have  to  be  increased  by  CH^  each,  so  that  the  most  complicated 
kephalin  might  contain  44  atoms  of  carbon.  None  of  these  hypotheses 
explain  either  the  deficiency  of  hydrogen  or  the  excess  of  oxigen 

/  Ci,H,A  (kephalyl)  ) 


■-C,3H3,NPO,  +  aq. 



(namely,  as  compared  to  the  theory  derived  from  chemolysis)  in  the 
various  kephalins  and  their  compounds  which  have  been  analysed, 
and  of  which  the  following  is  a  synopsis  : 

Kephalin  (empirical  formula)  -  C^2^79^^^i:r 
Kephalin,  perhaps  -       -       -    C42HgJ»NPOg  +  5H.p. 
Kephalin  cadmium  chloride    -    C42H^9NPOj3  +  CdCl^. 

(dissociates  partially  in  watery  reagents.) 

^''^Sm Srid'e"™'!        }  2(C,,H,,NP0„  +  HCl)  +  Pt  CI,. 
Kephalin  with  amido-kephalin  |  C^2Hg,^N.^POj3. 

(mixture)       -       -       -  j  2(C^2H79NPOi3. 
Oxykephalin  cadmium  chloride  C42HK9NPOJ4  +  CdCl^. 
Peroxykephalin     -       -       -  C42H;9NPOif^. 
Peroxykephalin,  diplumbic     -  C^g^^^s^^^^P^r/ 
Kephaloidin  -       -       -       -  C^^H^^NPOig. 

^""^^chbrtde^^^         cadmium  J  2(C^2Hr5NPO,,)  +  CdCl2. 

There  is  little  doubt  of  the  existence  of  a  dinitrogenised 
kephalin,  termed  amidokeplialin,  which  was  mixed  to  the  extent 
of  one-third  nearly  with  a  preparation  of  kephahn  met  with  in 
the  course  of  the  researches.  This  body  is  less  soluble  in  ether 
than  kephalin.  It  is  probably  constituted  analogously  to  the 
amidomyelin  described  in  a  special  chapter.  But  as  this  amido- 
kephalin  has  not  been  finally  examined,  I  am  unable  to  give  any 
further  data  concerning  it. 

Of  the  decomposition  products  of  kephalin  by  chemolysis,  I 
have  already  mentioned  Irj^halojihosphoric  acid,  under  the  non- 
nitrogenised  monophosphatides.  Kephalk  acid  is  the  principal 
chemolytic  product  of  the  process,  in  w^hich  the  phosphatide  is 
almost  entirely  severed.  All  its  salts  are  soluble  in  ether  and  in- 
soluble or  little  soluble  in  alcohol.  It  assumes,  in  the  free  state 
or  in  combination,  a  brown  colour,  from  which  it  has  not  yet  been 
possible  to  free  it  by  any  known  process.  The  formulae  which 
can  be  constructed  for  the  acid  vary  between  Cj()H3203,  and 
CJYH28O3,  or  CjwH3y03,  and  CJ-H32O3.  They  are  mainly  derived 
from  barium  scdts,  which  contain  from  18-28  per  cent,  to  20*05  per 
cent.  Ba.  in  some  cases  19  "29  per  cent,  to  19-89  per  cent.  Ba. 
The  kephalates  of  barium,  of  calcium,  and  of  lead,  are  brown 

Another  chemolytic  product  of  kephalin  is  stearic  acid,  of 



melting-point  69*5  ;  this  was  examined  in  the  free  state,  and  as 
l)arium  and  lead  salt. 

Stearic  acid  -       -  - 

Barium  stearate     -       -  '2{(^^^.^.fi.^'Edi. 

Lead  stearate        -       -  2{Q^^^fi^)Vh. 

Grlycerophosplioric  acid  was  isolated  from  kephalin  as  lead  salt, 
calcium  salt,  CgH^CaPO^j,  and  in  the  new  form  of  add  calcium  salt, 
C^^Hi^^CaP20i2 ;  as  barium  salt,  CgH^BaPOg  ;  this  could  be 
obtained  crystallised,  monohydrated,  and  as  alcoholohydrate,  in 
which  latter  state  one  molecle  of  acid  glycerophosphate  of  barium, 
composed  similarly  to  the  acid  calcium  salt,  contained  at  least 
three  molecles  of  alcohol  and  six  of  water. 

Kephalin  further  yielded  neurin  and  another  base,  perhaps 
derived  from  the  former.  The  second  base  in  amidokephalin  was 
not  ascertained. 

The  third  subdivision  of  this  subgroup  is  represented  by 
paramyelin,  a  phosphatide  which  contains  probably  glyceryl, 
neuryl,  and  an  oleo-cholide  radicle  hitherto  unknown.  It  strikes 
with  oil  of  vitriol  and  sugar  syrup  an  immediate  deep  purple 
colour ;  the  mixture  of  acids  obtained  by  chemolysis  with  barita 
does  the  same  in  a  more  intense  manner.  Paramyelin  is  a  white, 
firm,  solid  body,  crystallising  from  boiling  spirit  in  plates  and 
needles.  It  combines  with  cadmium  chloride,  and  the  solubility  of 
this  compound  in  hot  benzol,  and  its  insolubility  in  cold  benzol, 
afford  facilities  for  the  isolation  of  the  body.  A  specimen  of 
cadmium  chloride  salt  from  human  brain  gave  on  preliminary 
analysis  Cg^H^gNPOg  +  CdCl^;  another  from  oxbrain, 
CggH^gNPOg  +  CdCl2.  It  is  not  maintained  that  these  com- 
pounds were  unitary  and  did  not  contain  an  admixture  of  a  small 
quantity  of  one  or  more  principles  similar  to  paramyelin,  i.e., 
paramyelins  differing  from  each  other  in  the  item  of  the  second 
acid  radicle.  Paramyelin  also  forms  a  hydrochl orate  platino- 
chloride  salt. 

While  lecithin  and  paramyelin  exhibit  mainly  alkaloidal 
functions,  and  kephalin  shows  alkaloidal  and  acid  functions  on  a 
wide  area,  the  fourth  subdivision  or  species  of  the  mononitrogen- 
ised  monophosphatides,  the  myelins,  exhibit  mainly  acid  properties. 
The  representative  myelin  is  a  firm  compound,  and  combines  with 
lead  like  a  dibasic  acid  ;  that  is  to  say,  admits  a  didynamic  atom 
of  lead  in  place  of  two  atoms  of  hydrogen.    On  the  other  hand,  it 


does  not  combine  with  cadmium  chloride  as  do  lecithin,  kephalin, 
paramyelin,  amidomyelin,  and  s25hingomyelin.  This  peculiarity 
seems  to  indicate  a  peculiar  constitution,  of  which,  without  ex- 
haustive chemolyses,  no  account  can  be  given,  but  which  may  be 
such  as  to  necessitate  the  separation  of  myelin  from  the  other 
three  members  of  the  subgroup,  and  its  allocation  to  a  subgroup, 
of  which  it  would  be  the  peculiar  representative.  Myelin  and  its 
compounds  on  analysis  have  jdelded  the  following  formulae  : 

Myelin  in  lead  salt    -       -       -  C^^H^-NPOk). 
Myelin  free       -       -       -       .  Cgc^HlNPOg. 
Myelin  lead      .       -       .       .  C.I.H^gPbNJPOiy. 

There  may,  perhaps,  be  myelins  varying  in  carbon  from  39  to  44 

I  now  come  to  the  subgroup  of  dinitrogenised  monopJiosphatldes,  of 
which  I  had  given  a  preliminary  notice  in  my  researches  of  1874 
under  the  name  of  amidomyelin  and  apoDiijelin,  but  of  which  the 
former  has  been  isolated  only  latel}^,  while  the  latter  has  been 
more  fully  investigated,  and  classified  with  a  body  isolated  and 
investigated  under  the  name  of  sphingomyelin.  Amidomyelin 
completely  bore  out  the  theory  of  the  composition  which  I  had 
assigned  to  certain  compounds  of  mixtures  of  brain-educts  with 
platinum  and  cadmium  chloride  ;  out  of  such  mixtures  amido- 
myelin on  the  one,  and  lecithin  and  paramyehn  on  the  other  hand, 
were  isolated  first  as  compounds,  afterwards  in  the  free  state.  If 
any  argument  were  needed  to  justify  the  analyses  of  the  mixtures 
alluded  to,  analyses  to  which  no  fairminded  inquirer  would  attribute 
any  other  character  than  that  of  reconnoitring  proceedings,  the 
success  which  has  been  induced  by  their  results  would  be  sufti- 
cient.  Apomyelin  was  found  to  be  a  genuine  educt  and  imme- 
diate principle  of  the  brain. 

Of  amidomyelin  I  have,  therefore,  practically j^roved  the  existence 
and  individuality  by  direct  isolation  and  analysis.  But  I  have 
not  had  time  to  ascertain  anything  about  its  constitution  by 
chemolysis  of  the  pure  substance.  There  are,  however,  some  data 
available  for  a  preliminary  view  of  at  least  some  of  the  radicles 
likely  to  be  met  with  in  the  l)ody,  in  a  research  on  the  chemolytic 
products  of  a  cadmium  precipitate,  which  in  the  relative  research 
I  have  described  as  the  principal  cadmium  salt. 

Amidomyelin  is  analogous  to  sphingomyelin  and  apomyelin  in 
this,  that  it  contains  two  atoms  of  nitrogen  upon  one  atom  of 



phosphorus ;  these  two  atoms  of  nitrogen  are  disposed  in  two 
different  radicles,  and  influence  the  character  of  the  compound  so 
that  it  presents  itself  as  a  diacidic  base,  or  a  dipolar  alkaloid.  In 
the  latter  quality  it  combines  with  cadmium  chloride  in  two  ratios, 
the  fully  saturated  compound,  which  is  that  most  commonly  ob- 
tained, containing  a  little  more  than  30percent.  of  cadmium  chloride. 

Amidomyelin  has  been  proved  to  exist  in  five  forms,  one  of 
isolation,  four  of  combination. 

Amidomyelin    -       -       -       -       -  C^^HggN^PO,,. 
Amidomyelin  hydrochlorate       -       -    C44HggN2P09  +  HCl. 
Amidomyelin  monocaduiium  chloride  -    C^^HggNgPOf,  +  CdClg. 
Amidomyelin  dicadmium  chloride      -    C^^HggN.^POc,  +  2(CdCl2). 
Amidomyelin   hydrochlorate  platinum  ^  2(C44HggN2P09  +  HCl) 
chloride     -       .       .       .       -    \      +  PtCl^. 

The  second  subgroup  of  the  diamidated  monophosphatidcs  in- 
cludes sphingomyelin  and  ajjomyelin.  Sphingomyelin  has  been 
much  studied  and  chemolysed,  and  has  given  not  Only  the  funda- 
mental information  upon  which  the  hypothesis  of  the  phosphatides 
is  based,  but  also  the  first  knowledge  of  a  number  of  compound 
radicles  new  to  science.  It  is  not  maintained  that  the  knowledge 
of  the  bodies,  acids,  alkaloids  and  alcohols,  in  the  shape  of  which 
they  appear  after  chemolysis  of  the  principle,  is  definitely  roui^ed 
off.  For  in  its  prosecution,  conditions  of  the  utmost  difficulty  and 
complexity  were  met  with,  arising  mainly  from  homology  and 
isomerism.  Thus  one  product  was  a  fatty  acid  of  the  composition 
expressed  by  the  formula  CigHg^jO^,  being  the  third  isomer  of  stearic 
acid  discovered  in  my  researches,  sphingostearic  acid,  fusing  at  57°, 
therefore  at  almost  the  same  interval  below,  as  the  second  isomer 
of  stearic  acid,  namely,  neurostearic  acid,  fusing-point  84°,  fuses 
above  the  fusing-point  of  ordinary  stearic  acid,  which  latter  melts 
at  69*5'^.  It  is  evident  from  this  that  henceforth  a  fatty  acid 
from  the  brain  can  be  diagnosed  neither  by  its  elementary  com- 
position alone,  nor  by  its  melting-point  alone,  but  that  a  know- 
ledge of  both  is  required  to  approximately  fix  its  nature ;  an 
accurate  diagnosis  requires  the  knowledge  of  all  physical  and 
chemical  properties  and  of  reactions.  More  particularly  a  mere 
melting-point  determination  of  a  sample  of  fatty  acid  from  the 
brain  has,  by  itself,  no  diagnostic  value  whatever,  and  particularly 
can  no  longer  be  used  in  the  attempt  to  make  out,  by  the  well- 
known  tables  of  Heintz,  the  quantities  of  different  ingredients  in 


mixtures  of  which  certain  melting-points  are  supposed  to  be 
accurate  exponents. 

How  wonderfully  the  phenomenon  of  isomerism  complicates 
brain  research  and  biological  research  in  general  will  become  still 
more  apparent  by  the  following.  Another  product  of  the 
chemolysis  of  sphingomyelin  is  an  alcohol,  sphingoid  of  the 
empirical  formula  Ci^HjgO,  or  C^gHg^^O^,  which,  on  the  supposition 
that  the  latter  formula  expressed  its  atomic  weight,  would  be  the 
fourth  isomer  of  stearic  acid. 

A  third  product  of  the  chemolysis  of  sphingomyelin  is  an 
alkaloid  closely  resembling  the  sphingosin  of  the  cerebrosides, 
Cj^Hg^NOo,  but  showing  a  little  more  carbon  and  hj^drogen,  so  as 
to  answer  to  the  formula  CqH^^NO^.  To  these  three  radicles,  a 
molecle  of  neuryl,  C^H^^O,  is  yet  attached,  so  that  on  the  basis 
of  its  chemolysis  we  are  able  to  attribute  to  sphingomyelin  three 
somewhat  different  formula?  of  constitution,  in  each  of  which  three 
terms  are  certain,  while  of  the  remaining  two  terms  one  is  certain 
as  regards  its  percentic  composition,  but  uncertain  as  regards  its 
atomic  Aveight ;  while  the  other,  namely  the  second  nitrogenised 
radicle,  is  not  yet  sufficiently  well  defined  to  afford  much  aid  to 
synthetical  calculations.  The  smallest  formula  gives  a  total  of 
CgoHjQ^N^PO^,  while  the  largest  leads  to  a  formula  with  61  Carbon; 
but  all  empirical  formulae  for  sphingomyelin,  which  we  shall  have 
to  consider  below,  lead  to  the  necessity  of  assuming  the  presence 
in  the  free  body  of  a  few  atoms  of  water,  which  are  not  accounted 
for  by  the  sum  of  the  products  of  the  chemical  cleavage. 

It  is  certain  that  the  smallest  formula  just  given,  and  which  is 
almost  identical  with  the  formula  for  apomyelin  formerly  given,  is 
only  a  type,  and  that  there  are  varieties  in  which  either  the 
alkaloid  or  the  fatty  acid,  or  the  alcohol  differ  from  those  just 
formulated  probably  by — hCH^,  or  — hnCH^.  The  increase  in 
CH^  of  the  alkaloid  obtained  by  chemolysis  beyond  the  quantities 
demanded  by  the  formula  of  sphingosin  may  be  due  to  the  admix- 
ture of  a  small  quantity  of  a  body  being  a  compound  of  sphingol, 
CigHg^O,,  and  sphingosin,  Cj^H.-NO^, ;  total,  C3^H6c,N03  +  H.p. 
If  all  these  data  are  constant,  then  we  cannot  doubt  that  the 
limits  of  error  are  confined  between  very  small  dimensions. 

The  typical  sphingomyelin  crystallises  well  in  microscopical 
plates,  combines  with  cadmium  chloride  in  two  ratios,  the  com- 
pounds being  crystalline,  and  gives  up  one  nitrogenised  radicle 



on  limited  chemolysis,  namely  the  loosely  bound  neurin,  C-H^gNO, 
leaving  an  acid  which  contains  all  the  phosphorus  of  the  sphin-- 
gomyelin  together  with  half  the  original  nitrogen,  and  in  which, 
therefore,  N  :  P=l  :  1.  The  formula  of  the  acid,  a  produced 
mononitrogenised  monophosphatide,  from  the  C53  sphingomyelin 
is  C4gN95NPOj2,  and  its  name  may  be  sphlngomyelic  acid. 

The  following  is  a  synopsis  of  the  bodies  belonging  to  this 
subgroup  and  their  compounds  and  chemolytic  products  : 


Sphingomyelin  (ox)  -       -       -       .    C52Hio4]N'2POc)  +  H.p. 
Apomyelin  (man)     -       -       -       -  C^^H^QgNgPOg. 
Sphingomyelin  (theory  from  chemolysis)  C^gHj^gNgPO^  +  2H2O. 
Sphingomyelin  cadmium  chloride      -  C5jHc)()N2PO^Q-f-CdCl2. 

Do.         dicadmium  chloride    -    C5iHj,9N2POio  + 2(CdCl2). 

JDerivates  by  Chemolysis. 

Sphingomyelic  acid  -       -       -       -  C4gH95NPOi2. 

Sphingosin       -----  CJWH35NO2. 

Base  (as  sulphate)    -       -       -       -  2(C2o'H4iN02) +  H2S0^. 

Sphingol  ------  CigH3g02  or  CgH^gO. 

Sphingostearic  acid  (m.p.  57°)  -       -  C^gH^gO.,. 

Neurin     ------  CgH^^NO. 

Nitrogenised  product        -       -       -  C.^^HggNO,,. 

Phosphoric  acid        -       -       -       -  H3PO4. 

The  diamidated  phosphatides  yield  hydrochlorates  which  crys- 
tallise from  anhydrous  solvents  in  the  presence  of  excess  of  acid  in 
exquisite  form  and  purity ;  but  they  are  not  stable  in  the  pre- 
sence of  watery  reagents,  and  yield  hydrochloric  acid  to  solvents 
at  every  recrystallisation,  so  as  to  become  almost  free  from  the 
acid  by  mere  repetition  of  this  process.  When  the  hydrochlorates 
are  produced  from  the  cadmium  salts,  they  are  of  course  mixed 
with  double  the  quantity  of  hydrochloric  acid  necessary  for 
neutral  salts  ;  and  at  this  point  great  care  is  required  so  to 
manage  the  necessary  warming  of  the  mixture,  that  the  salt  may 
be  formed  without  any  very  great  part  of  it  being  chemol3^sed 
under  the  influence  of  the  redundant  hydrochloric  acid. 

The  diphosphatide  to  which  I  have  already  alluded,  in  which 
N  :  P  =  2  :  2,  and  to  which  I  have  given  the  name  of  assurin  (from 
the  Assyrian  God),  has  in  its  platinum  chloride  compound  the 
formula  C4gH94N2P209.  It  is  at  present  the  most  phosphorised 
body  of  this  class  known,  while  one  of  the  least  i^hosphorised, 


relatively  to  the  nitrogen,  is  a  phosphatide  educed  from  the  bile 
.as  a  crystallised  platinum  chloride  ealt  in  which  N  :  P  =  4  :  1, 
and  which  has  a  formula  by  which  it  is  characterised  as  a  tetra- 
polar  alkaloid,  the  four  basic  poles  corresponding  to  the  four 
nitrogenised  radicles  with  which  the  body  is  endowed. 

Thus  I  have  shown  that  the  phosphorised  educts  of  the  brain 
are  a  class  of  bodies  with  numerous  genera,  each  genus  having 
again  species  and  varieties ;  that  they  are  of  greatly  varying  chemi- 
cal construction  and  function,  and  that  the}^  are  so  distributed  as 
to  show  that  the}^  are  specifically  concerned  in  the  most  intimate 
parts  and  processes  of  protoplasmic  life. 

The  presence  of  water  diminishes  the  number  or  avidity  of 
affinities  in  all  phosphatides ;  it  combines  itself  with  these  bodies 
in  a  peculiar  manner,  by  which  they  show  their  character  as 
colloids,  and  it  afterwards  dissolves  them,  some  in  a  perfect,  others 
in  a  peculiar  and  imperfect  manner.  When  this  hydric  colloida- 
tion  is  at  a  maximum,  the  tendencies  to  decomposition  seem  to  be 
at  a  minimum.  The  watery  solutions  do  not  decompose  in 
stoppered  bottles  for  many  months  ;  only  after  six  months  some 
specimens  so  kept  showed  signs  of  decomposition  or  putrescence. 
It  seems  therefore  that  water  satisfies  some  of  those  affinities,  and 
what  is  most  remarkable,  its  influence  increases  and  diminishes 
with  the  mass  which  is  present  and  capable  of  acting,  so  that  it 
displaces,  when  in  quantity,  other  combinants,  but  when  these 
other  combinants  prevail,  water  is  itself  displaced,  and  the  colloid 
state  instantly  disappears.  In  the  dilute  watery  solutions  of  the 
phosphorised  bodies  therefore  almost  every  reagent  soluble  in 
water,  when  added  in  a  certain  excess,  produces  a  precipitate, 
which  contains  the  reagent  in  combination.  But  when  water,  or 
any  watery  solvent  capable  of  dissolving  the  combined  reagent,  is 
brought  in  contact  with  the  compound,  the  compound  imme- 
diately dissociates ;  the  reagent  passes  into  the  water, jort.!)'^//. 
as  the  phosphorised  body  passes  into  the  hydrated  colloid  state, 
and  if  the  influence  of  the  water  is  continued  by  renewal,  the  pi-o- 
cess  terminates  by  a  complete  separation  ;  the  phosphorised  body 
is  again  free  and  pure,  and  swells  and  dissolves  as  at  first. 

The  reagents  with  which  the  phosphorised  bodies  are  thus  able 
to  combine,  and  from  which  they  are  dissociated  by  water,  are 
acids,  alkalies,  and  salts.  The  phosphorised  bodies  therefore 
possess  alkaline  affinities  (for  acids),  acid  affinities  (for  alkalies), 



alkaloid  affinities  (for  salts) ;  all  those  affinities  are  overcome  by 
water  in  quantity,  but  the  affinities  for  water  are  overcome  by 
some  metallic  oxides,  such  as  of  lead,  copper,  manganese,  iron, 
and  even  to  a  slight  extent  by  lime  and  potash ;  these  latter 
compounds  are  dissociated  only  by  strong  mineral  acids,  and  the 
compounds  can  then  be  dialysed  out.  All  other  combinants 
separated  by  water  alone  can  be  completely  removed  from  the 
phosphorised  substances  by  dialysis  on  vegetable  parchment. 

We  have  therefore  here  a  diversity  of  affinities  such  as  is  not 
possessed  by  any  other  class  of  chemical  compounds  in  nature  at 
present  known  ;  and  the  exercise  of  these  affinities  being  greatl}^ 
influenced  by  the  mass  of  reagent,  and  the  mass  of  water  which 
may  be  present,  the  interchange  of  affinities  may  produce  a  per- 
fectly incalculable  number  of  states  of  the  phosphorised  and 
consequently  of  brain-mattei'.  This  power  of  answering  to  any 
qualitative  and  quantitative  chemical  influence  by  reciprocal 
quality  or  quantity  we  may  term  the  state  of  labile  equilibrium  ;  it 
foreshadows  on  the  chemical  side  the  remarkable  properties  which 
neuroplasm  exhibits  in  regard  of  its  vital  functions. 

From  this  it  also  follows  that  neuroplasm  (if  only  as  charac- 
terised by  the  phosphorised  bodies)  must  yield  obedience  to  every, 
even  the  slightest  external  chemical  influence,  which  may  reach  it 
by  way  of  the  blood.  It  must  take  up  metals,  acids,  salts,  alka- 
lies, and  alkaloids  presented  by  the  blood  ;  it  can  retain  only 
oxides  when  the  serum  is  again  free  from  the  combinants ;  a 
watery  serum  will  wash  the  brain,  a  more  watery  one  will  make 
it  swell  and  displace  mechanically  within  physiological  limits 
what  it  can  ;  a  still  more  watery  one  will  make  the  brain  dropsical 
and  produce  some  of  the  conditions  of  mechanical  j^ressure  on  the 
brain.  All  these  processes  are  the  necessary  consequences  of  the 
affinities  of  the  phosphorised  substances,  and  these  being  known, 
the  phenomena  could  be  predicted,  if  they  were  not  sufficiently 
known  as  phenomena,  though  hitherto  destitute  of  an  explanation. 
Thus  the  so-called  brain-fungus,  the  continued  protrusion  of  brain- 
matter  through  apertures  of  the  skull  produced  by  mechanical 
injuries,  may  in  certain  cases  find  a  physical  explanation  in 
simple  excessive  hydration  of  the  phosphorised  (and  nitrogenised) 
principles,  producing  general  intra- cranial  pressure. 

These  few  examples  show  that  the  acquisition  of  chemical 
statics  leads  almost  necessarily  and  very  easily  to  chemical  d^aia- 


iTfiics  of  the  brain  ;  and  these  will  in  their  turn  furnish  data  for 
physiological  and  pathological  conclusions.  But  these  deducive 
arguments  must  be  most  sparingly  and  cautiously  used,  until  the 
statics  are  in  a  state  of  perfection  and  completeness.  To  argue 
too  far  from  incomplete  data  would,  seeing  the  history  of  biolo- 
gical chemistry  during  the  last  thirty  years,  be  a  deplorable  error. 

The  NITROGENISED  NONPHOSPHORISED  substances  of  the  brain 
imitate  in  many  respects,  but  with  little  intensity,  the  properties  of 
the  phosphorised.  Thus  some  have  the  affinity  for  water  to  the 
extent  of  swelling  to  gelatinous  masses,  but  they  do  not  go  to  the 
state  of  apparent  solution,  and  do  not  pass  paper  filters  under  any 
l^ressure.  Some  are  insoluble  in  ether,  cold  benzol,  cold  alcohol, 
some  soluble  ;  all  dissolve  in  hot  benzol  or  alcohol,  and  are  depo- 
sited on  cooling  almost  entirely.  Therefore  as  compared  to  the 
phosphorised  bodies,  their  chemical  character  is  slight  solubility ; 
from  their  hydrated  colloid  state  they  are  also  reduced  to  a  more 
compact  and  combined  one  by  many  acids,  alkalies,  and  salts,  and 
they  retain  many  oxides  in  combination.  Water  has  the  same 
dissociating  influence  upon  these  as  upon  the  compounds  of  the 
phosphorised  principles.  The  nitrogenised  bodies  are  all  firm 
compounds,  and  do  not  easily  oxidise  or  decompose.  Their 
atoms  show  very  little  tension ;  but  they  possess  substitution 
poles,  where  hydrogen  is  replaceable  by  metalloids,  or  com2:>ound 
radicles ;  their  compounds  with  salts,  oxides,  or  acids,  are  so  un- 
stable as  not  to  admit  at  present  of  quantitative  definition. 

This  group  includes  six  great  subgroups,  of  which  the  first 
four  have  a  great  number  of  features  in  common,  while  the  two 
last  subgroups  are  dissimilar  to  the  former,  and  much  more 
simple  as  regards  chemical  constitution. 

The  first  subgroup  is  that  of  the  cerebrosides,  or  bodies  which 
contain  a  peculiar  sugar,  cerehrose,  in  which  different  radicles  of 
acids  and  alkaloids  (it  is  not  known  whether  of  alcohols  also,  in 
some  cases)  are  inserted.  Thus,  of  phrenos'ut,  C^^H^gNOg,  the 
definition  and  formula  of  constitution  are  the  following  : 




The  derivates  by  chemolysis  and  synthesis  of  products  are  the 
following : — Cerebrose,  a  crystallised  sugar,  isomer  of  glucose,  and 
like  this  dextrorotatory,  reducing  copper  solution,  and  tasting 
sweet,-  of  formula  C^3Hj206  ^  Neurodearic  acid,  an  isomer  of  stearic 
acid,  fusing  at  84",  of  formula  CjgH3,302 ;  Neurostearic  ether, 
C^qH^qO^,  or  {C.flrJ)C-^^'H.ofi.2^  produced  during  chemolysis  of 
phrenosin  in  alcohol  by  sulphuric  acid,  can  be  distilled  unchanged 
in  vacuo;  Sphingosm,  an  alkaloid,  C^-Hg^NO^ ;  as  sulphaie, 
2(Cj-H35N02)H2SO^,  insoluble  in  absolute  alcohol  ;  or  hydro- 
chlorate,  Cj-Hg^NO.^HCl,  soluble  in  water ;  Psychosm,  C^gH^^NO^ 
being  the  cerebroside  of  sphingosin,  a  body  having  alkaloidal 
properties,  but  less  pronounced  than  those  of  sphingosin  ;  .^Esthe- 
sin,  a  compound  of  sphingosin  and  neurostearic  acid  less  water, 
Cg.H^gNOg.  Under  the  influence  of  heat  phrenosin  yields  a 
caramel,  C^^Hk-^NO^,  by  the  loss  of  four  molecies  of  water  ;  by  a 
similar  reaction  psychosm  also  yields  a  caramel  of  the  formula 
C03H.3K.NO.3 ;  these  caramels  are  brown,  insoluble  in  spirit,  soluble 
in  ether. 

Synopsis  of  cerebrosides  and  derivates : 

Phrenosin  (educt)-  -  -  -  C^^H^j^NOg. 
Derivate  by  dehydration;  caramel  -  C^jH-^NO^. 
Derivate  by  substitution :  Nitrited  /  C^iH^gN^Ojg,  or 

phrenosin  nitrate  -    "    -       -  (  C4iH^g(N02)NOg  +  HN03. 

Derivates  by  cleavage  {chemolysis)  and  synthesis  of  products  : 

Cerebrose    -----  C^Hj^O^^. 

IN eurostearic  acid-       -       -       -  C^gHgcO.,. 

Ditto  ether       '  -       -       -       -  O.^^Yi^fi.^  or  {^"^■2^r;)^i^'^;fP->; 

Sphingosin  -       -       _       _  C\-H35N02. 

Ditto  sulphate     -       -       -       -  ^(Cj.R.^NO.,) +  H2S0^. 

Ditto  hj/drochlorate     -       -       -  Ci^Hg^NO^-f  HCl. 

Psychosin    -----  C.gH.^NO:. 

Caramel  of  psychosin    -       -       -  C.23H3^N03. 

The  second  cerebroside,  and  accompanying  phrenosin,  is 
kerasin,  a  body  crystallising  in  microscopic  filamentous  masses, 
which  are  very  voluminous,  and  enclose  mechanically  great 
volumes  of  spirit.  Although  the  knowledge  of  this  body  has 
been  greatly  advanced  lately  by  the  discovery  of  processes  for  its 
separation  from  sphingomyelin,  and  more  particularly  from  a  body 
which  I  shall  describe  later  under  the  name  of  binosin,  yet  cir- 
cumstances did  not  allow  me  to  finally  fix  hy  chemolysis  its 
rational  constitution  in  the  same  manner  as  this  has  been  done 



for  phrenosin.  Kerasin  may,  like  phrenosin,  comprise  a  number 
of  analogously  constituted  bodies,  of  which  the  most  probable 
formulae  are  : 

Psychosin  (as  sulphate)      -       -    2(C,.3H^.^NO-)  +  H.^SO^. 
Cerebrose  -----  CgH^o^G- 
Fatty  acids  of  the  formula  -       -  CnH^nO.,. 

Both  kerasin  and  phrenosin  are  neutral  bodies,  and  do  not  com- 
bine with  acids,  alkalies,  and  salts  in  stoichiometric  proportion. 

The  cerehrinacides,  or  cerebrin  bodies  which  combine  with  lead 
and  other  bases,  are  as  yet  little  known.  They  will  yet  require 
long  and  important  researches^  not  only  because  they  are  numerous, 
but  more  particularly  because  they  occur  mixed  with  a  class  of 
sulphurised  bodies,  of  which  I  give  a  preliminary  sketch  below.  It 
is  probable  that  the  first  cerebrinacide  to  be  considered — namely, 
cerehrinic  acid — ma}^  be  a  cerebroside,  in  which  three  hydroxy]  s  are 
replaced  (in  phrenosin  and  kerasin  only  two  hydroxy  Is  are  thus 
replaced),  two  by  fatty  acid  radicles,  one  by  an  alkaloid  radicle. 
The  fact  that  cerebrinic  acid  became  dehydrated  like  phrenosin 
under  the  influence  of  heat,  assumed  a  brown  colour,  lost  its  solu- 
bility in  spirit,  and  acquired  a  new  solubility  in  ether — in  short, 
that  it  became  changed  in  the  same  manner  as  a  saccharide  is 
changed  when  it  passes  into  a  caramel — supports  this  surmise. 
Whether  others  of  the  cerehrinacides  are  cerebrosides  can  at  pre- 
sent be  neither  asserted  nor  denied.  Several  of  the  cerehrinacides 
which  have  been  isolated,  such  as  spherocerebrin  and  the  (accord 
ing  to  quantity)  principal  cerebrinacide,  are  distinguished  from 
the  cerebrosides  and  cerebrinic  acid  by  their  containing  a  much 
larger  proportion  of  oxygen  than  these  bodies.  The  following  is 
a  synopsis  of  these  bodies  as  far  as  they  are  isolated,  together  with 
their  preliminary  emj^irical  formulae  : 

Cerebrinic  acid     -       -       .       .  C3,)H^j..N0.,. 

Caramel  of  cerebrinic  acid     -       -  Cr,„H^or.^Q3- 

Spherocerebrin     .       .       -       -  C.j.Hjo.,NOj-. 

Cerebrinacide,  principal        -       -  C^rjHjjgNO^j. 
There  are  a  number  of  subordinate  cerehrinacides  waiting  for 
closer  investigation. 

Educfs  : 




Prod  acts  h)i  cJienioIj/sis  : 



Of  the  cerebrosulphatides  I  have  hardly  done  more  than  demon- 
strated the  existence.  No  representative  body  has  been  isolated 
to  the  extent  of  being  free  from  phosphorus  and  cerebrinacide ; 
indeed,  it  must  remain  a  question  whether  there  are  not  bodies 
which  contain  sulphur  and  phosphorus  at  the  same  time.  The 
most  concentrated  preparation  of  cerebrosulphatide  which  I  have 
succeeded  in  producing  contained  4  per  cent,  of  sulphur. 

We  now  progress  to  the  consideration  of  an  entirely  new  series 
of.  bodies,  which  are  so  constituted,  and  exhibit  such  properties, 
that  they  may  perhaps  be  described  as  nitrogenisecl  fats  or  amiclo- 
lipotides.  Although  they  occur  mixed  with  the  cerebrosides,  never- 
theless they  are  at  once  demonstrated  not  to  be  such  by  the  low 
amount  of  oxygen  which  they  contain.  Of  these,  the  first  is 
hregenin  (from  the  Low  German  '  bregen,'  head  or  brain),  which  is 
easily  soluble  in  cold  ether,  crystallizes,  and  has  the  formula 
C^oHg^NO..  The  second  one  is  krlnosin  (from  the  Greek  word  for 
hair,  the  wavy  crystals  resembling  a  mass  of  tangled  long  hair), 
CggH-^NOg,  insoluble  in  cold,  easily  soluble  in  boiling  ether. 
Homology  of  these  two  bodies,  which  is  suggested  by  a  comparison 
of  the  formulae — 

may  not  be  assumed,  as  the  one  with  the  higher  number  of  carbon 
atoms  fuses  at  a  much  lower  temperature  than  the  one  with  the 
lesser  number  of  carbon  atoms. 

Of  the  group  of  alkaloids  occurring  in  the  brain,  hypoxanthin  and 
its  compounds  were  known  to  science,  but  isolated  with  greater 
precision  from  brain,  particularly  by  the  aid  of  phosphomolybdic 
acid.    The  following  bodies  were  produced  and  analysed  : 

Hypoxanthin  -       -       .  -  C^H^N^O. 

Ditto  hydrochlorate  -       -  -  C5  H^N^O  +  HCl  +  H2O. 

Ditto  with  platinum  chloride  -  '2{C^H^^fi  4-  HCl)  +  PtOl^. 

Ditto  nitrate    -       -       -  -  C5H4N4O  +  HNO.,. 

Ditto  with  silver  nitrate  -  -  C^H^N^O -f  AgN63. 

Ditto  with  silver     -       -  -  CgH^N^O  +  Ag^. 

The  other  alkaloids  contained  in  the  brain  are  either  much  more 
complicated  or  more  simple  than  hypoxanthin.  I  have  distin- 
guished these,  pending  further  inquiry,  the  second  alkaloid  as 
gladioUn,  and  the  third  alkaloid  as  tennysin ;  and  regarding  them 
little  more  can  be  stated  than  the  methods  by  which  they  were 

Bregenin  - 
Krinosin  - 



isolated,  and  the  elements  of  which  they  seem,  empirically,  to  be 
composed  : 

Gladiolin  (second  alkaloid)  ^i^H^QNgOg. 
Ditto  hydrochlorate  2:old  )  n  xr  at      ■  -rrrn  ■  a  r^^ 
chloride      -       -       _|CiAoNA  +  HCl  +  AuCl3. 

Tennysin  (third  alkaloid)  C.3H5NO. 

The  amidoacids  and  amides,  represented  by  leycin  and  allied  lyr'in- 
riples,  and  tyrosin,  bodies  otherwise  well  known  in  science,  were 
isolated  from  healthy  brain  for  the  first  time  in  the  course  of 
these  researches  : 

Leucin    -  -  -  -  C,5Hi.,N02. 

Tyrosin  -  -  -  -  CyHiiNOg. 

Urea  was  isolated  from  brain  and  cerebrospinal  fluid,  particu- 
larly in  disease.  In  cases  of  cholera  I  found  that  the  cerebrospinal 
fluid  contained  as  much  urea  as  healthy  human  urine — namely, 
about  2  per  cent. 

The  group  of  oxigenised  nonnitrogenised pinc'iples  consists  mainly 
of  alcohols  and  organic  acids.  The  alcohols  have  very  slight  com- 
bining powers.  The  most  prominent  of  these,  as  regards  both 
quantity  and  appearance,  is  cholesterin.  Discovered  originally  in 
human  gallstones,  and  erroneously  believed  to  be  a  fat,  this  prin- 
ciple received  the  inappropriate  name  which  hides  its  significance 
and  character.  Insoluble  by  itself  in  water,  it  is  probably  dis- 
solved in  neuroplasm  by  means  of  the  phosphorised  substances. 
Its  bearing  is  therefore  governed,  and  its  role  determined  to  a 
great  extent,  by  these  matters.  But  its  intrinsic  chemical  dynamis 
is  probably  also  independent  to  some  extent,  as  its  atomic  weight 
is  very  high.  As  an  alcohol  it  is  monodynamic,  and  if  it  did 
combine  with  acid  radicles,  naturally  would  therefore  give  rise  to 
one  class  of  ethers  only.  If  such  compounds  exist  in  the  brain, 
they  must  be  in  a  state  of  high  atomic  tension,  and  fall  to  pieces 
by  the  mere  fact  of  the  application  of  solvents. 

Some  data  seem  to  point  to  the  existence  of  a  second  alcohol 
by  the  side  of  cholesterin,  and  isomeric  or  homologous  to  it,  but 
the  hypothesis  lacks  definite  proof.  I  have  sometimes  found 
cholesterin  fusing  at  137°,  the  point  at  which  some  earlier  writers 
supposed  cholesterin  always  to  fuse.  But  since  the  fusing-point 
of  the  principal  cholesterin  is  certainly  145^,  the  lower  fusing-j^oint 
of  ViT  may  belong  to  an  isomer  or  homologue,  and  this  I  propose 
to  term  jjhrenoster in.  .  . 



The  bodies  which  may  conveniently  be  considered  as  forming  the 
subgroup  of  carhohydrates  are  inosite,  the  isomer  of  dextroglucose, 
discovered  in  and  bearing  its  name  from  muscle,  and  glijcogm, 
discovered  in  the  liver  and  other  organs.  It  has  seemed  to 
me  that  the  inosite  from  human  brain  was  somewhat  different 
from  that  of  the  ox;  at  least,  while  the  latter  easily  gave  a  com- 
pound with  cupric  oxide  of  the  formula  C^^H^.^O^  +  3CuO  +  SH^O, 
the  former  gave  no  such  precise  combination,  and  reacted  in  a 
peculiar  manner.  Some  have  supposed  inosite  to  be  the  material 
from  which,  by  a  post-mortem  metabolism,  the  lactic  acid  of  the 
bjain  took  its  origin.  But  since  it  has  been  shown  by  others  that 
inosite  by  ferments  yields  ordinary  zymolactic  acid,  whereas,  as  I 
have  shown,  the  lactic  acid  of  the  brain  is  always  and  exclusively 
the  optically  active  paralactic  or  sarkolactic  acid  originally  dis- 
covered in  flesh,  this  apprehension  has  become  obsolete. 

The  names  and  formulae  of  the  bodies  belonging  to  this  sub- 
group are  the  following : 

Cholesterin,  m.p,  145°  - 
Phrenosterin,  m.p.  137°  - 
Inosite  -  -  -  - 
Ditto  tricupric  trihydrate 

CgHi^O^  +  3CuO  +  3H2O. 

The  subgroup  of  the  nonnitrogenlsed  organic  adds  is  represented 
by  at  least  four  different  principles — formic^  sarkolactic,  succinic, 
and  a  tribasic  acid  which  may  perhaps  be  termed  oxyglyceric. 
Formic  acid  is  present  in  such  small  quantity  only  that  it  can  just 
be  recognised  in  the  distillate  by  reactions.  But  sarkolactic  acid 
occurs  in  quantities  up  to  1  per  mille  of  the  fresh  brain  substance. 
It  was  thus  possible  to  subject  this  body  to  a  more  intimate  study, 
and  describe  its  properties  with  great  precision.  Succiiiic  acid  was 
separated  and  identified  in  a  satisfactory  manner.  The  fourth 
acid,  oxyglyceric,  was  isolated  and  studied  mainly  by  the  aid  of  its 
silver  salt.  The  following  is  a  synopsis  of  these  acids,  their  for- 
mulae, and  some  of  their  compounds  : 

Formic  acid     _       _  .  _  CH.fl.^. 

Sarkolactic  acid       -     '  -  -  CgH^^O^ 

Ditto  zinc  salt,  hydrate  -  -  Zn(C.3H503)^-}-(H20),. 

Ditto  calcium  salt,  anhydrous  -  CaiCgH^Ogig. 

Succinic  acid    -       -  -  -  C^HgO^. 

Oxyglyceric  acid      -  -  -  CgHgO^. 

Ditto  silver  salt,  tribasic  -  -  CgH^Ag^O^. 


The  alhminous  siibstances  of  the  brain  may  be  considered  as 
nitrogenised  sulphatides,  inasmuch  as  sulphur  is  an  essential  con- 
stituent ;  if  bodies  like  casein  were  present  in  brain,  as  has  been 
supposed  by  some  inquirers,  they  might,  like  the  casein  of  milk, 
be  true  nitrogenised  sidphatide-phospliatides ;  if  connective  tissue 
were' present,  it  would  perhaps  come  under  neither  definition. 
These  substances  are  as  yet  very  little  known,  for  they  could  be 
examined  with  advantage  only  after  all  the  substances  described 
in  the  foregoing  pages  were  known  and  could  be  separated.  But 
in  this  process  the  albuminous  bodies  undergo  such  important 
alterations  that  the  difficulty  of  their  study  is  thereby  only  altered 
in  kind,  but  not  diminished  in  amount.  With  due  consideration 
to  this  circumstance,  they  were  in  the  first  instance  studied  by 
chemolysis,  and  have  yielded  very  remarkable  results.  The  deri- 
vates  by  chemolysis  included  the  following  : 

Albuminol  CigH^^NO,.  (?) 

Volatile  sulphurised  body 

Ammonia    and    compound    am-  (  -^rjj 

monias  -----  j  s- 
Carbonic  acid  -  -  -  -  CO^. 
Fatt}^  acid  -       -       -       -  .    -  —  — 

Oxalic  acid  -----  C.^H^O^. 
Phosphoric  acid  -       -       -       -  H.^PO^. 
Sulphurous  acid  -       -       -       -  SO.^. 
Acetic  acid  -----  CH^O.^. 

Leucein  -  -  -  C^H.^NO,. 
Second  alkaloid  -       -  CToHor.N.,0- 

Alkaloids  i  ^^^^^^^^  ^irvaiui^  -  - 

\  Do,  copper  compound  -    0^2-^23^^^!^'^  3^7- 

\  Third  alkaloid   -  -   

Leucin        -       -       -       -       -  C^H^.^NO^. 
Ditto   co2:)per  compound,   mono- )  .^/q      -j^q  ^q^^ 
cupric  dileucin-       -       -       .\-\^vi     2/  • 
Glycoleucin,  isomer  of  leucin       -  C^.Hj3]SI02. 
The    cupric    compound   is    also  \ 

isomeric  with  the  cupric  com-  >  2(C,;Hj2NO.,)Cu. 
pound  of  leucin       -       -       .  j 
Tyrosin      -----  C9Hi,N03. 
Tyrosin  mercurous  chloride  i^er- (  jj  ^.j, 

curie  oxyde     -       -       -       _  j    v  9   10     .5       &    /  •  o 

With  this  li£t  the  number  of  products  is  by  no  means  exhausted. 
Only  few  quantations  have  as  yet  been  made,  so  that  the  materials 
for  drawing  any  conclusion  regarding  the  constitution  of  the  albu- 
minous substances  of  the  brain  are  not  yet  to  hand. 


The  inorganic  ingredients  or  mineral  substances  of  the  brain  are 
distributed  amongst  its  juices  and  solid  ingredients  in  a  very  re- 
markable manner,  as  will  be  discussed  more  fully  below.  These 
bodies  were  formerly  studied  by  means  of  analyses  made  on 
materials  obtained  by  combustion  of  the  brain  as  a  whole.  This 
proceeding  had  two  sources  of  fallacy  connected  with  it,  which 
greatly  diminished  the  value  of  its  results.  In  the  first  place,  the 
phosphoric  acid  produced  by  the  destruction  of  the  phosphatides 
(in  which,  of  course,  phosphoric  acid  is  in  organic  combination) 
was  calculated  as  mineral  phosphoric  acid,  it  being  found  partly 
in  combination  with  bases,  partly  free.  Owing  to  its  being  in 
excess  over  the  whole  of  the  saturating  power  of  the  bases,  it  ex- 
pelled all  volatile  acids,  such  as  carbonic,  and  sulphuric,  and 
chlorine,  and  was  not  even  itself  entirely  preserved  from  the  re- 
ducing influence  of  the  glowing  charcoal,  which  volatilized  a 
portion  of  it  as  phosphorus.  This  inconvenience  was  only  partially 
avoided  by  the  use  during  combustion  of  caustic  baryta  or  barium 
nitrate.  In  fact,  by  no  method  as  yet  proposed  could  the  sulphur 
or  phosphorus  in  organic  comUnation  be  kept  separate  from  that  in 
inorganic  combination.  Some  progress  has,  however,  been  made 
by  the  separation  of  the  soluble  educts  from  the  insoluble  ones, 
and  from  the  interstitial  juices  ;  and  as  each  of  these  complex  sub- 
stances retains  mineral  matters  peculiar  to  itself,  while  the  phos- 
13hatides  can  be  almost  completely  excluded  by  precipitation  with 
acid  from  their  solution  or  suspension  in  water,  it  is  feasible  to 
obtain,  by  a  minimum  of  three  sets  of  analyses,  some  insight  into 
the  nature  and  distribution  of  the  mineral  ingredients  of  the 
brain.  I  enumerate  the  elements  which  enter  into  their  com- 
position : 

Metals:  sodium,  potassium  (ammonium),  calcium,  magnesium, 
iron,  manganese,  copper. 

Metalloids :  chlorine,  sulphur,  phosphorus,  carbon,  oxygen, 
hydrogen,  fluorine. 

There  is  met  with  at  almost  all  steps  of  the  separation  of  the 
ingredients  of  white  matter,  a  substance  distinguished  by  fusibility 
and  insolubility  in  boiling  alcohol,  which  was  named  stearoconote, 
and  regarding  which  a  few  explanatory  notes  may  properly  be 
given  in  this  place.  When  white  matter  is  placed  into  a  quantity 
of  hot  alcohol,  most  cholesterin  and  lecithin  and  some  cerebrin 
dissolve ;  but  the  other  phosphorised  and  nitrogenised  matters 


immediately  fuse  into  a  plaster-like  mass,  which  is  then  practically 
insoluble  in  boiling  alcohol.  There  is  therefore  here  an  attraction 
produced  by  the  fused  state  which  removes  the  solubility  of  some 
of  the  ingredients  of  the  mass  in  alcohol.    When  the  principal 
matters  soluble  in  ether — i.e.,  the  kephalins — are  now  extracted, 
the  fusibility  is  diminished,  and  some  of  the  cerebrins  dissolve 
more  freely  in  hot  alcohol.    Stearoconote,  however,  still  forms, 
and  is  now  a  reaction  mainly  of  the  myelins  and  the  cerebrosides. 
When  all  the  myelins  are  separated  from  the  cerebrin  group  of 
bodies,  their  power  of  forming  stearoconote  is  depressed  to  a 
minimum,  but  not  entirely  removed.    The  myelins  by  themselves 
also  retain  this  tendency  of  forming  a  fused  mass  insoluble  in 
boiling  alcohol,  which  in  the  text  has  been  termed  a  tendency  to 
stearoconotise.    The  phenomenon  seems  to  be  compound,  and  not 
simple,  and  to  consist  in  essence  in  a  dehydration  without  attendant 
change  in  quantities  of  atoms  of  other  elements.    For  T  have  found 
that  some  stearoconote  free  from  phosphorus  could,  by  treat- 
ment with  benzol  and  a  little  hydrochloric  acid,  be  transformed 
into  a  soluble  substance,  which  on  elementary  analysis  was  found 
to  have  the  same  empirical  composition  as  the  stearoconote  from 
which  it  was  made.    In  this  case  no  separation  of  a  base  from  the 
substance  could  be  proved  to  have  taken  place.    In  other  cases  it 
was  found  that  the  stearoconote  obtained  its  solubility  in  alcohol 
without  the  intervention  of  acids,  by  standing  in  benzol,  in  which 
it  is  easily  soluble.    In  a  third  class  of  cases  the  stearoconote  re- 
gained its  solubility  in  boiling  spirit  by  prolonged  treatment  with 
hot  or  boiling  water.    Again,  in  other  cases  it  was  probable  that 
the  stearoconote  was  really  a  compound  of  some  nitrogenised  body 
with  a  mineral  base,  and  bodies  resembling  the  stearoconotes  in 
some  respects,  but  not  in  all,  were  produced  by  adding  bases  to 
solutions  of  the  cerebrin  series.    On  the  whole,  then,  '  stearo- 
conote '  does  not  seem  to  be  a  chemical  individual  differing  from 
the  other  bodies  described,  but  a  function  of  several  bodies,  which 
pass  into  that  state  by  a  molecular  change,  which  change  can  be 
made  to  retrograde  mto  the  originally  soluble  condition. 

The  function  is  a  result  of  chemical  and  physical  influences 
acting  simultaneously  (alcohol  and  heat),  and  is  apparently  not 
obtained  by  either  influence  separatel}^  Stearoconote  seems, 
therefore,  a  product,  and  not  an  educt ;  but  it  is  indirectly  im- 
portant, as  showing  that  there  is  some  peculiar  attraction  or 



mutual  influence  between  the  bodies  of  the  two  great  groups.  In 
white  matter  where  those  brain-principles  are  all  mixed  together 
nearly  in  their  original  proportions  (only  lecithin  being  much 
diminished  in  quantit}^),  the  above  influence  has  its  highest  in- 
tensity. The  function  diminishes  with  increased  separation — i.e., 
increased  purity  of  educts.  It  is  entirely  lost  in  some  of  the 
educts,  when  they  are  in  the  pure  state ;  thus  pure  kerasin  could 
by  no  means  be  made  to  yield  any  stearoconote.  But  it  remains 
with  others,  particularly  myelin,  paramyelin,  and  sphingomyelin 
in  the  pure  state,  and  is  evoked  when  they  are  subjected  to  the 
influence  of  heat  in  the  presence  of  a  quantity  of  alcohol  insuffi- 
cient to  dissolve  the  whole  of  the  material  before  it  has  had  time 
to  fuse.  Once  fused,  it  seems  to  resist  solution,  even  after  re- 
peated powdering  to  increase  the  surface  for  the  action  of  alcohol, 
to  the  extent  of  being  rather  destroyed  than  dissolved. 

In  the  phenomenon  just  described  we  observe  as  the  main  result 
diminished  or  suspended  solubility — that  is  to  say,  suspension  of 
the  lowest  form  of  chemical  attraction.  In  a  phenomenon  now  to 
be  pointed  out,  we  j^erceive  however,  on.  the  contrary,  the  produc- 
tion or  elicitation  of  a  solvent  power  of  a  kind  hitherto  quite 
unknown  in  animal  chemistry.  Some  of  the  phosphorised  bodies, 
when  combined  with  certain  metals  or  metallic  salts,  in  the  pre- 
sence of  ethylic  ether,  and  whether  dissolved  in  it  or  not,  cannot 
be  separated  from  these  metals  by  hydrothion.  The  dissolved 
compounds  assume  the  colour  of  the  respective  sulphide,  and  re- 
main dissolved ;  the  compounds  insoluble  in  ether  immediately 
pass  into  solution  when  the  hydrothion  gas  is  passed  through  the 
mixture.  Thus,  cadmium  chloride  compounds  dissolve  with  a 
canary-yellow  colour ;  platinum  chloride  compounds  with  a  dark 
brown  colour  ;  lead  compounds  with  a  red  or  blackish-red  colour. 
The  compounds  can  be  partially  or  entirely  precipitated  by  water, 
or  alcohol,  or  ammonia,  etc.  They  contain,  in  addition  to  the 
phos2:)horised  body,  in  the  cases  of  chlorides,  chlorine  and  sulphur, 
besides  metallic  sulphide  ;  in  the  case  of  metals  like  lead,  metallic 
sulphide  and  sulphur.  Their  complication  places  them  at  present 
beyond  the  reach  of  stoichiometric  treatment. 

When  once  thus  combined  with  sulphur  (or  hydrothion)  and 
metallic  sulphide,  or  with  these  and  chlorine  in  addition,  and  pre- 
cipitated and  isolated,  the  phosphorised  bodies  can  by  no  means 
ordinarily  at  hand  be  again  obtained  in  the  free  state.    The  com- 


pounds  with  metals  of  the  phosphorised  bodies  can  be  decomposed 
by  hydrothion  only  while  suspended  in  water  or  spirit  :  the  pro- 
duct, a  mixture  of  metallic  sulphide  with  the  respective  body, 
must  then  be  extracted  by  a  suitable  solvent. 

The  obstacles  which  these  extraordinary  properties  of  the 
chemical  principles  of  the  brain  throw  in  the  way  of  chemical 
i:)rocedure  are  perfectly  indescribable.  To  use  a  simile  from 
military  life,  the  biologist  who  attacks  his  problem  in  front  is 
beaten  off  at  all  points ;  he  can  only  conquer  it  by  flanking  on 
long  and  circuitous  routes,  and  by  the  use  of  instruments  of 
warfare  which  are  either  new  or  superior  to  those  hitherto  in 

These  difficulties  increase  with  every  step  which  leads  nearer  to 
the  consummation  of  the  purpose,  and  are  greatest  at  the  point 
where  the  isolated  chemical  individuals  are  to  be  freed  from  the 
last  traces  of  admixed  impurity.  The  very  peculiarities  of  the 
principles  described  are  mostly  negations  of  the  properties  ordin- 
arily relied  upon  as  criteria  of  chemical  purity.  On  this  matter  I 
have  repeatedly  dilated  .in  the  text,  and  given  expression  to 
apprehensions  as  well  as  to  considerations  calculated  to  remove 
them.  As  the  difficulties  arose  they  were  followed  out  experi- 
mentally, one  by  one,  step  by  step,  to  the  exhaustion  of  the 
known  means  at  hand,  or  of  the  new  means  that  could  be  devised 
in  the  time.  But  it  must  be  left  to  the  future  to  increase,  if 
possible,  both  the  means  of  producing,  and  also  the  criteria  for 
insuring,  that  absolute  purity  of  ultimate  educts  which  is  the  con- 
dition of  certainty  in  chemical  science. 

It  is  therefore  not  asserted  that  the  absolute  limits  of  the 
subject  have  anywhere  been  reached ;  but  it  is  confidently  be- 
lieved that  its  entirety  has  been  explored  in  such  a  manner  that 
fundamental  truths  cannot  have  escaped  observation,  and  that 
what  remains  to  be  done  is  essentially  of  the  character  of  detail, 
which,  however  vast  by  multiplicity  it  may  become,  will  not  alter 
the  broad  outlines  which  this  investigation  has  led  me  to  state. 

While,  then,  there  may  be  some  degree  of  uncertainty  as  to  the 
absolute  purity  of  some  of  the  principles  involved,  there  can  be 
none  as  to  their  striking  individuality  ;  and  as  regards  this,  the 
positive  evidence  of  their  peculiar  and  distinctive  qualities  is  so 
strong  that  the  fact  of  their  not  uniformly  answering  to  certain 
other  criteria  is,  in  my  opinion,  quite  insignificant. 



By  the  researches  embodied  in  this  treatise  the  brain  is  shown 
to  be  the  most  diversified  chemical  laboratory  of  the  animal  body ; 
it  is  shown  that  all  other  organs,  even  when  the  results  of  their 
chemical  action,  be  they  destined  to  take  a  centripetal  or  centri- 
fugal course,  are  added  to  them,  are  relatively  much  more  simple 
and  very  much  less  specific  in  their  chemical  constitution  than  the 
organs  producing  and  conducting  nerve-power. 




Preparation  and  Coinminution  of  Bmintissue, — Anyone  who 
would  i^roceed  to  an  extensive  chemical  investigation  of  the  brain 
should  procure,  in  the  perfectly  fresh  state,  and  with  the  perfect 
freedom  from  disease  which  are  indispensable,  such  a  supply  of 
material  from  the  human  subject  as  will  suffice  for  his  purpose. 
Human  brains  are  not  only  relatively  the  largest  in  size,  but  also 
the  richest  in  specific  ingredients,  and  therefore  the  most  advan- 
tageous objects  of  inquiry.  But  they  are,  under  ordinary  circum- 
stances, difficult  to  obtain,  and  therefore  for  large  and  more 
general  inquiries  ox  brains  may  be  used.  Five  such  brains  weigh 
on  an  average  1,780  g,  or  eight  weigh  six  pounds.  They  are 
washed  once  and  freed  from  clotted  blood.  They  are  next  care- 
fully skinned,  the  arachnoid  and  pia  mater  being  removed  by 
means  of  fine  anatomical  forceps.  When  the  brains  are  entire 
they  may  be  skinned  in  the  ordinary  anatomical  manner,  which 
employs  two  pairs  of  forceps,  worked  simultaneously  and  anta- 
gonistically by  both  hands  of  the  operator.  When,  however,  the 
brains  are  much  broken  up,  each  piece  must  be  held  in  one  hand 
while  being  freed  from  membranes  with  the  other.  The  skinned 
parts  are  again  rinsed  in  water,  and  then  placed  in  water  for  a 
short  time ;  next  placed  upon  a  sieve  to  drain,  and  then  sub- 
merged in  methylated  alcohol  of  85  per  cent,  by  weight  in  volume 
strength,  previously  purified  by  distillation  over  tartaric  acid. 
Great  care  is  necessary  to  supply  a  sufficient  amount  of  alcohol, 
so  that  the  brains  may  be  quickly  dehydrated  and  hardened. 
For  if  the  alcohol  is  too  dilute,  or  becomes  too  dilute  l)y  being 
insufficient  in  quantity,  the  brains  remain  soft  and  unworkable, 


and  decompose  with  a  fetid  odour.  For  the  same  reason  all 
brains,  before  submersion  in  alcohol,  must  be  broken  up,  or  sliced 
into  small  pieces,  so  that  they  can  be  easily  penetrated  by  the 
alcohol.  This  is  required  even  when  strong  alcohol  is  used,  as 
this  is  liable  to  harden  the  outer  shell  merely,  and  leave  the  inside 
of  the  brain  to  soften  and  decompose. 

The  washing  and  submersion  in  water  probably  remove  small 
quantities  of  extractives  and  soluble  salts,  besides  the  blood,  and 
must  therefore  be  carried  out  with  care.  The  solutions  so  ob- 
tained are  thrown  away,  but  the  alcoholic  solutions  in  which  the 
brains  have  been  hardened  are  purified  from  albumen  by  boiling 
and  filtration,  freed  from  spirit  by  distillation,  and  evaporated  to 
the  consistence  of  extracts  on  the  water-bath.  They  are  to  be 
considered  as  water-extracts,  and  are  mostly  free  from  specific 
brain  substances,  and  only  yield  extractives  and  salts  and  other 
matters,  which  will  be  described  in  the  relative  chapters. 

When  the  brains  are  well  hardened  in  the  alcohol,  which  fre- 
quently requires  the  repeated  removal  of  the  watery  spirit  and 
substitution  of  fresh  strong  spirit,  they  are  passed  through  a 
rotary  mincing  machine,  and  the  minced  portions  are  again  mixed 
up  with  strong  alcohol.  This  pulp  is  now  worked  through  a  very 
fine  hair  sieve,  having  144  meshes  to  the  square  inch,  and  each 
of  the  twelve  strands  of  hair  crossing  the  square  inch  in  one  direc- 
tion, being  composed  of  eight  single  horse  hairs ;  the  sieve  stands 
upon  a  glass-receiver  in  such  a  manner  that  it  cannot  move,  and 
no  matter  which  passes  the  sieve  can  be  lost.  The  trituration  on 
the  sieve  is  effected  by  a  strong  circular  brush,  which  is  rubbed 
over  the  sieve  by  the  hands  of  a  workman.  When  passed 
through  the  sieve  the  brain  is  in  the  state  of  a  very  fine  pulp  or 
purree^  and  is  ready  for  extraction.  All  other  modes  of  commi- 
nution which  have  been  recommended  are  less  useful  than  the 
foregoing  ;  they  are  either  inefficient  or  slow  and  laborious  ;  in 
particular,  trituration  in  a  mortar  with  a  pestle  is  very  inefficient. 
All  methods  of  comminution  which  do  not  reduce  the  brain  to  the 
finest  possible  pulp,  or  smooth  paste,  must  be  rejected,  as  from 
imperfectly  comminuted  brains  the  immediate  principles  are 
necessarily  most  imperfectly  extracted. 

Extraction  of  Prainpulp  and  Separation  of  Albuminous  or  Insoluble 
Matter,  White  Matter,  Buttery  Matter,  Last  Oihj  Matter,  and  Ultimate 
JFatery  Mother- liquor. — The  smooth  paste  of  brain-matter  is  now 


mixed  Avith  a  considerable  amount  of  alcohol  of  85  per  cent.,  and 
heated  in  a  well-tinned  large  sauce2:)an  over  a  gas  lamp  by  a  star- 
burner  or  any  other  heat  source,  while  being  stirred  with  a  wooden 
rod  without  intermission.  When  it  has  reached  the  temperature 
of  70°  the  mixture  is  removed,  and  immediately  poured  on  a 
filtering  cloth  stretched  and  tied  over  the  top  of  a  large  earthen- 
ware jar  or  pan.  The  filter  iy  covered  with  a  wooden  cover. 
When  the  liquid  has  percolated,  the  pulp  is  removed  from  the 
cloth  with  a  fiat  spoon,  and  again  placed  in  the  saucepan,  mixed 
with  spirit,  heated  to  70°  while  being  stirred,  and  again  placed 
upon  the  same  filter  as  before.  This  operation  is  repeated  in  all 
about  five  times,  when  the  brain-matter  is  exhausted  of  all  matters 
which  alcohol  at  that  temperature  will  dissolve.  The  matter  is 
now  tied  up  in  the  cloth  and  pressed  in  a  screw-press.  It  comes 
out  as  a  solid,  somewhat  elastic  cake  of  alhum'mous  or  insoluUe 
matter,  of  which  the  analysis  and  description  will  be  given  in  a 
future  chapter.  In  my  earlier  experiments  I  arrested  the  heating 
at  45°,  because  it  has  been  so  frequently  stated  that  when  brain- 
matters  are  heated  beyond  they  decompose.  But  since  I  know 
the  behaviour  of  the  isolated  brain-matters,  I  have  come  to  con- 
sider this  statement  as  unfounded.  Moreover,  there  is  a  consider- 
able quantity  of  cerebrin-like  matter  in  brain  which  is  not  at  all 
dissolved  by  spirit  at  45°,  but  is  taken  up  by  boiling  spirit,  as 
has  been  shown  in  Ann.  Chem.  Med.  i.,  1879,  258.  To  extract 
all  this  matter  it  is  necessary  to  boil  the  albuminous  matter  with 
spirit  for  many  hours  in  a  platinum  still,  with  a  condenser  attached, 
and  to  repeat  this  at  least  from  twelve  to  fourteen  times.  But 
the  low  heat  is  certainly  convenient,  and  need  not  therefore  in 
the  earlier  extraction  be  overstepped.  For  the  same  reason  a 
saucepan  of  cast-iron,  about  three  gallons  capacity,  is  preferable  to 
any  other  vessel  of  tin  or  glass.  The  earthenware  jars  or  pans 
should  be  of  a  capacity  of  from  twelve  to  fifteen  gallons.  I  have 
found  them  most  useful,  and  carried  on  all  operations  from  the 
soaking  and  hardening  to  the  last  filtration  of  the  buttery  preci- 
pitate with  their  aid. 

White  Matter. — The  alcoholic  extracts  are  all  united,  and  allowed 
to  cool  during  from  twelve  to  twenty-four  hours.  In  hot  weather 
the  cooling  must  be  assisted  by  placing  the  jar  in  a  tul)  and 
surrounding  it  with  cold  water  and  ice.  The  extracts  during 
cooling  deposit  a  large  amount  of  v-hite  cri/staliine  and  (jramdar 



prec'qntate,  which  adheres  to  the  sides  and  covers  the  bottom  of 
the  vessel,  while  the  alcohol  is  perfectly  clear,  though  coloured 
slightly  yellow.  The  whole  is  filtered  through  a  cloth  stretched 
over  a  pan,  and  when  the  entire  precipitate  is  collected  on  the 
cloth,  and  has  been  condensed  by  stirring  with  a  spoon,  the  cloth 
is  removed,  tied  up,  and  placed  in  the  screw-press,  and  all 
mother-liquor  thus  removed.  When  taken  out  of  the  cloth  the 
precipitate  presents  itself  as  a  hard  white  cake,  which  can  be 
broken  into  pieces,  and  constitutes  the  particular  white  matter  of 
Vauquelin,  and  will  in  the  text  be  signalised  as  tvhife  matter. 
When  the  abbreviations  fV.M.  occur  in  the  description  of 
any  preparation,  they  indicate  that  the  preparation  has  been 
extracted  from  this  white  matter.  I  shall  not  describe  this  white 
matter  any  further,  nor  have  I  instituted  any  experiments  upon 
it  such  as  Vauquelin  made,  because  it  is  evidently  a  very  compli- 
cated mixture,  containing  nearly  the  whole  of  the  substances  to 
be  described  as  the  cerebrosides,  stearoconotes,  cholesterins, 
kephalins,  myelins,  and  lecithins,  and  small  quantities  of  other 
matters.  The  processes  by  which  these  substances  may  be  ex- 
tracted will  be  given  lower  down,  after  the  description  of  the 
treatment  of  the  alcoholic  extract  has  been  completed.  Here  it 
may  yet  be  stated  that  the  white  matter  can  be  jireserved  in 
stoppered  bottles,  in  a  cool  place  and  protected  from  light,  almost 
unchanged  for  a  very  long  time,  In  contact  with  absolute  alcohol 
it  also  remains  unchanged,  though  gradually  yielding  a  yellow 
extract ;  but  in  contact  with  ether  it  yields  kephalin  to  the  latter, 
which  is  quickly  oxidised  into  a  red  substance  having  a  green 
fluorescence  ;  this  effect  seems  due  to  the  peroxide  of  hydrogen 
produced  during  the  oxidation  of  the  ether.  I  have  therefore 
limited  the  use  of  ether  to  the  most  necessaiy  02:>erations,  and 
then  cause  the  substances  to  pass  through  these  with  great 
despatch,  so  that  this  oxidising  effect  of  the  ether  is  as  far  as 
possible  avoided. 

BiiUery  Matter. — The  Alcoholic  Filtrate  from  the  Wldte  Matter 
now  placed  in  a  capacious  tinned  copper,  or  better  platinum  still, 
and  a  great  part  of  the  alcohol  is  distilled  off.  When  a  certain 
degree  of  concentration  has  been  obtained,  which  is  determined 
by  experience,  the  hot  liquid  is  thrown  into  a  pan,  and  again 
allowed  to  cool,  assisted  if  necessary  with  cold  water  or  ice.  It 
now  deposits  a  second  quantity  of  matter,  which  is  less  solid  and 


more  coloured  than  the  first,  and  after  filtration  remains  on  the 
cloth  as  a  semi-solid  plastic  substance,  to  which  I  have  given  the 
name  of  the  hidterij  matter.  This  can  only  be  freed  from  mother- 
liquor  by  manipulation  with  a  spoon,  and  must  not  be  pressed  too 
hard,  as  it  is  liable  to  pass  through  the  meshes  of  the  cloth.  The 
buttery  matter  consists  of  much  chole&terin,  lecithin,  little  myelin, 
kephaloidin,  and  some  cerebroside,  and  small  quantities  of  other 
matters  ;  the  substances  are  therefore  qualitatively  mainly  the 
same  as  in  the  white  matter,  but  they  are  present  in  entirely 
different  proportions.  The  buttery  matter  also  keeps  well  in  a 
bottle  by  itself,  or  in  the  presence  of  alcohol,  but  should  also  not 
be  kept  long  in  ether. 

Last  Oily  Matter. —  The  Alcoholic  Filtrate  from  the  Buttery  is  again 
distilled  so  long  as  good  spirit  passes  over  and  no  precipitate 
ensues  in  the  fluid.  When  these  conditions  are  exhausted  it  is 
placed  in  a  large  dish  on  a  water-bath  and  evaporated.  At  a 
certain  period  oily  drops  make  their  appearance,  which  adhere  to 
the  sides  or  float  in  the  fluid,  and  unite  to  larger  round  globular 
masses.  They  separate  easily  while  the  fluid  is  hot,  but  w^hen 
the  fluid  cools  they  swell,  become  flaky  and  distributed  in  the 
fluid,  and  cannot  be  filtered.  They  are  best  separated  while  hot 
by  a  separating  funnel,  to  which  they  adhere,  while  the  fluid  sinks 
down  ;  or  they  may  be  collected  on  a  paper  filter  on  a  hot  funnel. 
This  matter  has  received  in  my  laboratory  the  title  of  the  last 
oily,  hy  which  it  will  be  signahsed  in  this  essay.  It  consists 
mainly  of  phosphorised  bodies  with  little  cholesterin,  and  some 
peculiar  not  yet  accurately  defined  matters. 

Ultimate  Watery  Motherliqnor. — The  Filtrate  from  Last  0//// con- 
stitutes the  ultimate  icatei  y  mntherliquor  and  contains  all  matters 
from  the  brain  which  are  highly  soluble  in  water,  such  as  the 
salts,  the  extractives,  and  soluble  immediate  principles  to  be 
described.  This  liquid  is  evaporated  on  the  water-bath  to  the 
consistence  of  a  thin  extractive,  and  placed  in  bottles  until  further 
examined  as  will  be  described.  While  the  preparation  accumu- 
lates it  is  well  to  keep  the  extract  covered  with  some  absolute 
alcohol  to  prevent  the  formation  of  mould  on  its  surface. 

Process  for  sejjarativg  White  Matter  into  its  Constitvents. — The 
following  process,  which  for  the  purpose  of  alibrcviation  I  will 
term  '  ether  process,  W.M.,'  yields  the  cerebrins  very  quickly  and 
directly,  and  leaves  little  myelin,  some  paramyelin,  and  most 


sphingomyelin,  with  the  cerebrins.  It  also  yields  kephalin,  but 
much  remains  in  the  mother-liquors.  The  myelin,  lecithin,  and 
cholesterin  remain  in  the  ultimate  mother-liquor,  and  can  be 
separated  only  by  cadmium  or  platinum  chloride. 

The  white  matter  is  fully  extracted  with  ether  in  stoppered 
bottles,  with  the  precaution  of  using  the  same  ether  for  several 
portions  of  white  matter  so  as  to  obtain  saturated  solutions.  All 
secondary  solutions  and  washings  are  concentrated  by  the  still. 
For  this  purpose  French  flasks  and  a  platinum  condenser  are  used  ; 
the  flasks  contain  spirals  of  platinum-wire,  and  pieces  of  tobacco- 
pipe  tube  strung  on  platinum-wire.  This  arrangement  prevents 
bumping.  The  whole  of  the  solutions  are  now  exposed  in  bottles 
(stoppered)  to  a  strong  freezing-mixture  of  ice  and  salt,  and  the 
clear  coloured  ether  is  quickly  siphoned  off  the  dense  white 
deposit.  All  siphons  are  of  glass  tube,  with  movable  caoutchouc 
joints,  and  mounted  in  corks,  so  that  they  can  be  applied  to  the 
bottle  to  be  emptied  on  one  side  and  to  the  bottle  to  be  filled 
on  the  other  side,  air-tight,  and  be  started  either  by  blowing 
(with  the  air-bellows)  or  by  suction  at  the  opposite  end.  The 
inner  limb  of  the  siphon  is  so  curved  as  to  be  near  the  side  of  the 
bottle  and  easily  visible ;  its  end  is  directed  sideways  to  prevent 
an  upward  rush  of  deposited  matter. 

This  apparatus  gives  to  the  operator  full  power  to  start  and 
arrest  the  flow  of  the  ether  whenever  he  finds  it  desirable,  and 
enables  him  to  regulate  the  suction-pipe,  and  so  take  off  the  last 
portions  of  ether  above  the  deposit,  without  losing  much  ether 
or  being  molested  by  it.  When  the  principal  mother-liquor  is 
removed,  pure  ether  is  thrown  upon  the  deposit,  which  is  again 
frozen.  The  deposit  is  much  less  soluble  in  pure  ether  than  in 
the  mixture  of  dissolved  matters,  a  peculiarity  shown  by  almost 
all  brain-substances.  The  deposit,  when  dense,  frequently  forms 
a  firm  cake  at  the  bottom  of  the  bottle,  which  comes  off  as  a 
round  disk.  These  ^  fird  deposits  hy  frost  from  ether  extracts  of  white 
matter '  are  separated  into  sphingomyelin,  myelin,  and  other 
matters,  as  will  be  described  lower  down. 

When  the  ether  extracts  give  no  further  deposits  on  exposure 
to  renewed  freezing-mixtures,  they  are  treated  with  absolute 
alcohol  until  all  kephalin  is  precipitated.  If  the  alcohol  be 
watery,  even  slightly,  say  of  80  to  90  per  cent,  strength,  the 
deposit  contains  much   cholesterin,  particularly   if   the  ether 



solution  is  concentrated.  Absolute  alcohol  should  therefore 
be  always  taken  as  well  as  absolute  ether  for  these  operations  ; 
many  other  reasons  which  will  appear  in  the  sequel  support  this 
desideratum  to  the  extent  of  making  it  an  absolute  condition  of 
perfect  success. 

The  ether-alcohol  mother-liquor  is  now  distilled  for  removal  of 
the  ether,  and  is  then  while  hot  treated  with  a  hot  solution  of 
lead  acetate  and  ammonia  as  long  as  a  precipitate  is  thereby 
produced.  The  precipitate,  which  contains  kephalin-lead, 
myelin-lead,  and  a  few  other  compounds,  is  filtered  off.  The 
solution  is  allowed  to  cool,  and  deposits  more  lead  [salts  and 
cholesterin.  The  filtered  solution  is  again  distilled  while  carbonic 
acid  is  passed  through  it.  By  this  means  the  excess  of  lead  is 
precipitated  and  the  ammonia  expelled.  To  the  alcoholic  filtrate 
alcoholic  cadmium  chloride  is  now  added  as  long  as  a  precipitate 
is  produced,  and  afterwards  a  large  excess  of  the  same  cadmium 
chloride  solution.  The  precipitate  is  filtered  oflf  on  a  cloth  pressed 
hard,  and  immediately  placed  in  ether.  A  cadmium  salt  of  a 
phosphorised  matter  dissolves,  which  is  not  yet  very  well  defined. 
Cholesterin  also  dissolves.  The  greater  bulk  of  the  cadmium 
chloride  j)recipitate  remains  insoluble  in  ether,  and  consists  of 
lecithin,  paramyelin,  amidomyelin,  and  sphingomyelin,  all  com- 
bined with  the  metallic  chloride.  These  compounds  can  be 
separated  from  each  other,  and  the  immediate  principles  can  be 
isolated  from  the  compounds  by  processes  to  be  described. 

Treatment  of  the  Butter?/  Matter. — The  buttery  matter  is  dissolved 
in  hot  spirit,  and  completely  precipitated  with  hot  ammoniacal  lead 
acetate.  The  filtrate  is  allowed  to  get  cool  and  deposit  more  lead 
salt  and  cholesterin,  to  be  separated  hy  ether.  The  united  lead 
salts,  etc.,  after  exhaustion  by  ether,  are  treated  with  spirit,  etc., 
for  the  isolation  of  their  ingredients,  as  will  be  described  below. 
From  the  main  alcoholic  filtrate  the  excess  of  lead  and  ammonia 
are  removed  by  a  current  of  carbonic  acid  and  distillation.  To 
the  clear  filtrate  alcoholic  cadmium  chloride  is  added  in  large 
excess,  and  the  white  precipitate  is  treated  just  as  the  precipitate 
from  white  matter  above  described.  Ether  extracts  from  it 
cholesterin  and  a  phosphorised  cadmium  chloride  compound,  whiie 
the  part  insoluble  in  ether  is  separated  by  the  benzol  process  into 
three  or  four  compounds  of  lecithin,  jjaramyelin,  and  amido- 


Treatment  of  the  Last  Oily  Matter. — This  is  dissolved  in  hot  alcohol 
and  precipitated  by  lead  acetate  and  ammonia ;  the  precipitates 
formed  in  the  hot  fluid,  and  after  its  cooling,  are  collected  and  sepa- 
rated into  their  constituents  by  ether  and  spirit,  etc.,  as  will  be 
described.  The  spirit  is  freed  from  lead  and  ammonia  by  distil- 
lation with  the  aid  of  a  current  of  carbonic  acid.  The  filtered 
alcoholic  solution  is  precipitated  with  an  alcoholic  solution  of 
cadmium  chloride  added  in  large  excess,  and  the  cadmium  com- 
pounds are  collected  and  treated  as  will  be  described. 

Summary  of  Immediate  Principles  in  the  crude  state  or  Mixtures 
thereof  isolated. — We  have  thus  separated  the  brain  into  the 
following  immediate  principles  or  mixtures  thereof  : 

1.  First  extractives  (by  soaking  alcohol). 

2.  Insoluble  albuminous  residue. 

3.  White  matter,  containing — 

{a)  Kephalin  (with  varieties  and  compounds) ; 

(b)  Lecithin  (with  varieties  and  compounds)  ; 

(c)  Paramyelin  (with  varieties  and  compounds)  ; 

(d)  Myelin  (with  varieties  and  compounds); 

{e)  Amidomyelin  (with  varieties  and  compounds)  ; 
(/)  Cholesterin  and  phrenosterin  ; 

{g)  Cerebrin  mixture,  or  mixture  of  cerebrosides,  cere- 
brinacides,  cerebrosulphatides,  and  amidolipotides, 
containing  also  sphingomyelin  and  assurin. 

4.  Buttery  matter,  containing  — 

{a)  Kephaloidin  (with  varieties  and  compounds) ; 
{h)  Lecithin  (with  varieties  and  compounds) ; 
(c)  Paramyelin  (with  varieties  and  compounds) ; 
{d)  Myelin  (with  varieties  and  compounds)  ; 

(e)  Amidomyelin  (with  varieties  and  compounds) ; 

(/)  Sphingomyelin,  assurin,  cholesterin  and  phreno- 
sterin ; 

{g)  Cerebrin  mixture  (very  small  amount),  amidolipotides. 

5.  Last  oily  matter — 

{a)  Lecithin  ; 
(&),  Paramyelin  ; 

(c)  Oily  lipoid  matters,  cerebrols. 

6.  Ultimate  watery  extracts  of  brain,  containing — 

{a)  Alkaloids ; 

(h)  Amidoacids  and  imides  ; 

(c)  Carbohydrate  ; 

(d)  Organic  acids  and  salts  ; 

(e)  Liorganic  or  mineral  salts. 



Summary  and  Arrangement  in  Groups  of  Immediate  Principles. — 
In  the  foregoing  descriptions  of  processes  I  have,  for  the  purpose  of 
brevity,  spoken  of  the  crude  immediate  principles  which  were 
isolated  as  if  they  consisted  of  a  single  body  each  ;  but  in  the 
summary  list  just  given  I  have  added  to  most  of  the  names  of 
these  compounds  an  enlarged  definition,  by  which  not  only  the 
2mre  princi])le,  but  also  varieties  of  it  and  comjmmds  of  it  are  said 
to  have  been  isolated  in  one  and  the  same  operation.  This  is 
strictly  the  case,  as  will  be  seen,  for  example,  in  the  account  of 
kephahn  hereafter  to  be  given  ;  but  it  may  be  at  once  stated  that 
the  pure  immediate  principle  which  gives  rise  to  the  name  con- 
stitutes the  great  bulk  of  each  preparation,  that  this  bulk  is 
relatively  greatly  increased  by  the  removal  during  the  process  of 
purification  of  matters  in  chemical  combination  with  a  smaller 
portion  of  the  immediate  principle,  and  that  the  varieties  are  very 
similar  in  type  to  the  principal  matter,  and  whenever  they 
cannot  be  separated  absolutely  their  nature  and  quantity  can 
be  ascertained  by  very  good  approximations.  Where  matters  are 
so  similar  in  i3roperties  as  kephalin  and  kephaloidin,  a  complete 
separation  of  the  entire  quantity  of  each  from  the  other  is  not 
easily  eff'ected,  but  a  quantity  of  each  can  be  obtained  pure  from 
the  other,  and  from  the  results  obtained  by  their  chemical  study 
the  composition  of  mixtures  in  any  proportions  can  be  derived. 
The  immediate  principles  above  enumerated  may  be  arranged  in 
the  following  groups  : 

Group  of  Phosphorised  Principles  or  Phosphatides. 

Subgroup  of  Monoidtrogenised  Monophosphatides  (N  :  P  =  1  :  1)  : 

Kephalins ; 

(Sphingomyelic  acid,  a  product.) 

Suhgroiip  of  Dinitrogenised  Monophosphatides  (N  :  P  =  2  :  1) : 

Amidomyelins ; 
Amidokephalins  ; 
Sphingomyelins  (Apomyelins). 

Subgroup  of  Dinitrogenised  Dipkosphatide  (N  :  P  =  2  :  2)  : 



Subgroup  of  Nitrogenised  Phosphatide-sulpliatide  : 

Cerebrosulphatide,  body  from  group  of  cerebrinacides,  con- 
taining probably  phosphorus,  nitrogen,  and  sulphur  (?). 

Subgroup  of  Nonnitrogenised  Monopliosphatides  : 

First  acid  from  buttery  matter,  lipophosphoric  acid. 
Second  acid  from  buttery  matter,  butophosphoric  acid. 
(Kephalophosphoric  acid,  a  product.) 

Group  of  Nitrogenised  Nonphosphorised  Principles. 

Subgroup  of  Cerebrosides  : 
Phrenosin ; 

Subgroup  of  Cerebrinacides : 
Cerebrinic  acid  ; 
Sphaerocerebrin ; 
Other  principles  not  yet  defined. 

Subgroup  of  Cerebrosulphatides  : 

Body  containing  sulphur. 
Subgroup  of  Amidolipotides,  or  nitrogenised  fats  : 

Bregenin  ; 


Subgroup  of  Alkaloids  : 
Hypoxanthin ; 
Second  alkaloid,  gladiolin  ; 
Third  alkaloid,  tennysin. 

Subgroup  of  Amidoacids  and  Amides  : 
Leucin  and  homologous  principles  ; 
Tyrosin ; 

Group  of  Principles  composed  of  Three  Elements  only. 

Subgroup  of  Alcohols,  nonnitrogenised  : 
Cholesterin ; 
Phrenosterin  (?). 

Subgroup  of  Carbohydrates  : 
Inosite ; 
Glycogen  (?). 

Subgroup  of  Organic  A  cids,  nonnitrogenised  : 
Formic  acid ; 
Sarcolactic  acid  ; 
Succinic  acid ; 
Oxyglyceric  acid. 


Group  of  Albuminous  Substances. 

Subgroup  of  Nitrogenised  Sulphatide-pliospliatkles  : 
Plastin  ; 

Gangliocytin,  Cytophosphatide  (aNuclein). 

Stihgroup  of  Nitrogenised  Sid/phatides  : 
Albumen  ; 

Grou^  of  Inorganic  Frinciples,  including  both  acids  and  bases, 
and  salts,  either  free  or  in  combination  with  many  of  the  fore- 
going organic  principles.    This  comprises  : 
Sulphuric  acid ; 

Hydrochloric  acid,  and  chlorine  in  chlorides ; 
Phosphoric  acid  ; 
Carbonic  acid  ; 

Potash  \ 

Soda  I  In  combination  with  immediate  principles, 

Ammonia  I  forming  their  bases,  or  in  combination  with 

Lime  \  phosphoric  acid,  and  attached  to  immediate 

Magnesia  t  principles  as  phosphates,  or  in  combination 

Copper  I  with  mineral  acids,  as  free  mineral  salts  in 

Iron  I  the  juices  and  extracts. 

Manganese  J 
Alumina,  silica,  fluorine  (doubtful). 




General  Properties  of  the  Phosphorised  Principles. — This  group 
comprises  kephalin,  kephaloidin,  myelin,  sphingomyelin,  assurin, 
lecithin,  paramyelin,  amidomyelin,  and  their  congeners  and  com- 
pounds. All  these  bodies  have  certain  properties  in  common, 
which  point  to  some  similarity  in  chemical  constitution ;  by  other 
peculiarities,  again,  they  are  sharply  distinguished  from  each 
othei".  Some  are  soluble  in  water  in  a  certain  manner  and  measure. 
When  they  are  in  the  dry  state,  and  are  placed  in  pure  water, 
they  sink  to  the  bottom,  and  are  at  once  wetted  by  the  water. 
Thus  their  specific  gravity  is  shown  to  be  greater  than  that  of 
water,  and  by  this,  and  the  faculty  of  being  wetted,  they  are 
sharply  distinguished  from  the  fats  or  fatty  acids,  but  assimilated 
to  the  soaps,  as  the  older  authors  correctly  stated.  When  they 
have  remained  in  the  water  for  a  short  time  they  begin  to  swell, 
to  become  transparent  at  the  thin  margins  of  the  particles,  and 
covered  with  a  loose  layer  all  over  their  surface.  This  on  agita- 
tion is  easily  detached,  and  floats  in  clouds  in  the  liquid;  the 
clouds  diffuse  themselves  indefinitely  throughout  the  whole  of  the 
water,  and  if  enough  water  is  present,  the  mixture  is  frequently 
shaken,  and  some  time  is  given,  the  particles  of  solid  matter  dis- 
appear entirely  and  form  a  turbid  solution  of  very  peculiar  appear- 
ance. As  will  be  seen  hereafter  in  particular,  these  solutions  can 
by  no  mechanical  means  be  clarified ;  yet  they  are  solutions,  and 
pass  through  many  layers  of  the  finest  Swedish  filtering-paper. 
Most  particles  are  so  small  as  to  be  beyond  the  reach  of  optical 
definition  as  single  particles.  They  exhibit  their  presence,  how- 
ever, by  iridescence  in  the  case  of  myelin  and  lecithin,  and  by 


reflecting  polarised  light  in  all  cases.  These  solutions,  therefore, 
resemble  somewhat  the  cold  solutions  of  soaps,  and  the  emulsions 
produced  by  solid  fatty  acids  with  neutral  phosphates,  the  emul- 
sion produced  by  vegetable  seeds  (almonds)  with  water,  etc.  ;  but 
they  differ  from  milk  and  emulsion  of  fats  and  gum  by  there  being 
few  particles  visible.  Moreover,  emulsions  are  supposed  to  require 
the  presence  of  two  agents  besides  water,  whereas  these  brain 
substances  give  this  peculiar  solution  with  mere  water ;  they  are  not 
decomposed,  as  the  soaps  are,  into  acid  and  alkaline  salt,  as  they 
are  not  salts,  but  form  these  solutions  in  the  free  and  uncombined, 
but  also  in  the  combined  state.  I  can  give  no  better  definition  of 
this  peculiar  condition  than  by  describing  it  as  a  state  of  imperfect 
or  incomplete  solution,  a  stage  intermediate  between  the  solid  and 
the  fluid  state  of  matter.  Those  who  do  not  coincide  in  this  de- 
scription may  term  the  solution  an  'emulsion,'  if  that  conveys  any 
definite  idea,  or  a  state  of  the  finest  subdivision  of  particles,  with 
peculiar  attraction  of  these  particles  to  water,  and  consequent  re- 
pulsion of  particles  from  each  other.  This  latter  part  of  the 
question  I  shall  have  to  consider  at  greater  length  when  I  come 
to  discuss  the  dependence  of  the  structure  of  the  brain  upon  the 
chemical  and  physical  characters  of  its  ingredients.  For  the  pre- 
sent purpose  it  suffices  to  sum  up  that  these  phosphorised  bodies 
have  all  an  extreme  attraction  for  water,  swell  in  it,  and  ulti- 
mately form  a  nearly  perfect  solution.  Amidomyelin,  when 
obtained  by  dialysis  from  cadmium  chloride  salt,  forms  a  perfect 
solution,  which  filters  like  water,  but  congeals  by  warmth. 
Sphingomyelin,  when  quite  pure,  contracts  again  and  then  sinks 
in  water,  and  can  be  filtered  out  of  it.  By  this  means  they  afford 
good  opportunities  for  mechanical  and  chemical  purification  now 
to  be  described. 

Deposition  of  Impnrities. — The  solutions,  on  standing,  deposit 
any  mechanical  impurities,  and  any  cholesterin  contained  in  the 
matters  dissolving  crystallises  out  and  sinks  to  the  bottom.  Any 
excess  of  the  matters  beyond  saturation  is  also  deposited,  as  well 
as  the  less  soluble  compounds — e.g.,  sphingomyelin.  If  any  cere- 
brin  were  with  the  matters,  it  would  also  deposit.  All  solutions, 
tlierefore,  produced  as  above,  and  which  experience  has  shown  me 
should  not  contain  above  1  per  cent,  of  the  matters,  must  be 
allowed  to  stand  for  a  day  or  two,  in  order  that  these  insoluble 
impurities  and  admixtures  may  be  deposited.    The  pure  solution 


is  then  removed  with  the  siphon  from  the  deposit,  the  solution  is 
filtered,  and  the  deposit  further  exhausted  with  water. 

Filtration  of  the  Watery  Solutions  of  the  Plmphorised  Matters. — - 
When  the  solutions  are  placed  on  an  ordinary  filter  of  paper,  a 
portion  passes  by  gravitation ;  but  the  pores  of  the  paper  gradu- 
ally become  obstructed,  and  filtration  ceases.  It  is  therefore 
necessary  to  expedite  filtration  by  the  aid  of  pressure.  For  this 
purpose  I  have  constructed  a  new  apparatus,  in  which  a  vacuum 
draws  the  liquid  to  be  filtered  into  a  hollow  cylinder  surrounded 
with  paper. 

The  filter  is  a  hollow  cylinder  of  silver-plate  pierced  like  a  fine 
sieve,  and  covered  with  a  six-fold  roll  of  Swedish  or  Rhenish 
filtering- j)aper,  made  secure  at  the  top  and  bottom  by  a  ring  of 
string,  which  also  runs  spirally  over  the  whole  j^aper.  This 
stands  in  a  glass  cylinder,  which  contains  the  fluid  to  be  filtered, 
and  is  always  kept  full  by  a  perpetual  siphon,  drawing  the 
liquid  from  the  reserve  bottle ;  as  frequently  as  the  fluid  in  the 
wide  upper  part  of  the  cylinder  sinks  below  the  oblique  end  of 
the  air-tube,  which  is  wide  and  provided  with  a  bulb,  air  is 
admitted,  and  the  siphon  acts.  The  bottle  receiving  the  filtrate 
is  evacuated  of  air  gradually  by  means  of  the  air-pump.  The 
tube  which  draws  the  filtered  liquid  from  the  cavity  of  the 
cylinder  goes  to  the  bottom  of  the  cylinder,  so  that  nearly  the 
whole  of  the  filtered  liquid  can  at  any  time  be  drawn  into  the 

Such  a  cylinder,  about  a  foot  long  and  four  inches  in  cir- 
cumference, will,  with  a  pressure  of  70  centimetres  of  mercury, 
filter  a  Winchester  quart  full  of  1  per  cent,  solution  of  ]3hos- 
phorised  matter  per  day :  the  more,  the  purer  the  substance  is  ; 
the  less,  the  more  cholesterin  it  contains.  Sometimes  only  1 00  cc. 
are  filtered  per  hour.  In  such  a  case  a  coarser  filtering-paper 
should  be  rolled  over  the  Swedish,  to  collect  the  coarsest  particles 
and  prevent  them  from  getting  upon  the  Swedish  paper.  After 
some  hours  filtration  becomes  slow,  and  ultimately  ceases  entirely  ; 
then  the  paper  is  found  covered  with  a  gelatinous  mass  of  undis- 
solved matter  and  impurities.  These  may  be  rinsed  off  and  again 
extracted  and  filtered,  but  I  have  mostly  found  the  matter  so 
small  in  quantity  that  I  have  discharged  it  with  the  paper.  Such 
a  filter,  with  two  changes  of  paper  per  day,  may  be  going  night 
and  day,  and,  if  all  corks  are  air-tight,  which  is  easily  eff"ected  by 



applying  hot  paraffin  to  them,  requires  very  little  attention  except 
a  few  strokes  of  the  pnmp  from  time  to  time.  When  the  sub- 
stances previous  to  their  solution  in  water  were  very  pure,  they 
left  no  vestige  of  cholesterin  crystals  or  of  cerebrosides  on  the 
filter.  The  filtered  fluids  are  still  opaque,  those  from  kephalin 
more  coloured,  those  from  myelin  and  lecithin  of  a  milky  white- 
ness with  the  blue  iridescence.  When  a  good  filtration  had  been 
effected,  a  second  filtration  effected  no  improvement,  and  was 
quickly  accomplished.  In  this  manner  all  phosphorised  matters 
used  for  cardinal  preparations  were  passed  through  the  process  of 
watery  solution  and  filtration. 

The  process  offers  peculiar  advantages  for  each  of  the  three 
varieties  of  phosphorised  principles.  Kephalin  scarcely  ever  re- 
tains any  cholesterin,  but  myelin  always  does,  unless  it  has  passed 
through  the  PtCl^,  or  lead  process. 

SoluhUUy  of  Phosphorised  Matters  in  Ether. — Kephalin  dissolves 
in  this  reagent  in  almost  any  quantity ;  lecithin  only  less  than 
kephalin ;  but  myelin  is  very  little  soluble  in  cold  ether,  more  in 
hot  ether,  and  is  instantaneously  deposited  from  the  ether  as  it 
cools.    Sphingomyelin  behaves  in  a  similar  manner. 

Sohihility  of  Phosphorised  Matters  in  Alcohol. — Lecithin  dissolves 
in  all  proportions  in  hot  absolute  alcohol,  less  in  cold ;  kephalin  is 
almost  insoluble  in  cold  alcohol,  more  soluble  in  hot,  almost  en- 
tirely deposited  on  cooling;  myelin,  paramyelin,  amidomyelin, 
and  sphingomyelin  are,  however,  little  soluble  in  cold  alcohol, 
largely  soluble  in  hot,  and  deposited  on  cooling  in  a  crystallised 
state,  and  in  such  quantities  that  the  fluid  becomes  filled  with 
crystals.  It  will  thus  be  seen  that,  while  water  offers  no  means 
for  the  separation  of  these  substances  from  each  other,  ether  and 
alcohol  offer  great  advantages,  which  have  indeed  been  utilised 
in  the  construction  of  the  method  for  their  separation  above 

TIDES.    N  :  P  =  l  :  1. 


Definition. — Lecithins  are  phosphorised  and  nitrogenised  imme- 
diate principles  of  brain-tissue  and  egg-yelks.  There  are  three 
varieties  known,  all  containing  neuryl,  oleyl,  glyceryl,  and  a  third 


.acid  radicle  replacing  hydro xyl  in  the  phosphoric  acid ;  the  three 
varieties  differ  as  regards  the  third  acid  radicle. 

Isolation. — Lecithins  can  be  isolated  by  the  following  process  : 
The  alcoholic  extract  of  brain-matter  from  which  white  matter 
has  been  deposited  is  concentrated  until  on  cooling  it  forms  the 
deposit  called  buttery.  This  is  isolated  by  filtration,  re-dissolved 
in  warm  spirit  and  treated  with  lead  acetate  and  ammonia  as  long 
as  a  precipitate  is  produced,  and  filtered  hot.  The  filtrate  depo- 
sits a  crystalline  mixture  of  cholesterin,  lead  salts,  and  lecithin. 
This  mixture  is  again  isolated  by  filtration,  dissolved  in  hot 
spirit,  and  allowed  to  crystallise  again.  To  the  solution  filtered 
from  the  first  deposit  as  well  as  to  that  filtered  from  the  second 
crystals  an  alcoholic  solution  of  cadmium  chloride  is  now  added, 
as  long  as  a  precipitate  is  produced :  then  half  the  volume  of  the 
cadmium  chloride  solution  already  used  is  added  to  the  mixture. 
The  precipitate  is  isolated  by  filtration  and  dissolved  in  boiling 
spirit ;  the  solution,  filtered  hot,  is  allowed  to  deposit  the  salt, 
which  is  then  filtered  off.  This  is  a  mixture  of  three,  maybe 
four,  compounds,  one  of  lecithin  with  cadmium  chloride,  another 
of  paramyelin  with  the  same  salt,  a  third  of  amidomyelin,  and  a 
fourth  of  sphingomyelin  with  cadmium  chloride.  The  last  is,  if 
at  all,  present  in  the  smallest  quantity  ;  the  lecithin  and  ami- 
domyelin compounds  are  present  in  about  equal  quantities,  and 
constitute  the  grtat  bulk  of  the  precipitate.  The  precipitate  is 
dried  in  vacuo  over  sulphuric  acid  (when  dried  on  the  water-bath 
it  becomes  coloured),  finely  powdered  and  exhausted  with  ether. 
It  is  again  dried  and  powdered,  and  treated  for  the  separation  of 
the  several  compounds  as  follows  : 

The  dry  precipitate  is  suspended  in  a  large  volume  of  anhydrous 
benzol  and  frequently  stirred ;  kephalin  cadmium  chloride  and 
kephaloidin  cadmium  chloride  are  extracted  at  this  stage ;  the 
mixture  is  then  boiled  for  some  time  in  a  water-bath,  and  a  por- 
tion of  the  benzol  is  removed  by  distillation.  The  mixture  is 
now  allowed  to  stand  in  a  cold  place  for  twenty-four  hours,  and 
then  thrown  on  a  filter.  The  matter  remaining  on  the  filter  is 
subjected  to  the  same  treatment  with  fresh  benzol  as  often  as 
may  be  necessary  to  exhaust  it  of  all  matter  soluble  in  cold  benzol. 
The  matter  insoluble  in  cold  benzol  is  now  again  boiled  with 
benzol  and '  thrown  on  a  filter  kept  hot  by  a  steam-jacket.  A 
benzol  solution  now  passes  through  the  filter,  which  deposits  a 


compound  on  cooling,  and  keeps  little  or  nothing  in  solution. 
This  treatment  also  is  repeated  until  the  insoluble  compound 
yields  nothing  to  boiling  benzol.  The  cadmium  chloride  precipi- 
tate has  thus  been  separated  (leaving  the  kephalin  compounds  out 
of  consideration  for  the  present)  into  three  different  matters  : 

(1)  Compound  soluble  in  cold  benzol^  lecithin  cadmium  chlo- 


(2)  Compound  soluble  in  hot  benzol,  deposited  on  cooling, 

paramyelin  cadmium  chloride. 

(3)  Compound  insoluble  in  benzol,  cold  or  boiling,  amidomyelin 

dicadmium  chloride. 

As  sphingomyelin  is  somewhat  soluble  in  cold  alcohol,  it  is  to 
be  expected  that  a  small  quantity  is  present  in  the  mixture  of 
which  the  three  compounds  just  defined  are  the  principal  con- 
stituents. It  may  be  separated  from  the  amidomyelin  in  the 
manner  to  be  described  below.  But  its  presence  in  the  cadmium 
chloride  precipitate  from  buttery  matter  has  not  been  proved  ;  in 
the  process  of  separating  the  educts  by  solvents  only  it  remains 
mainly  if  not  entirely  with  the  cerebrosides  and  cerebrinacides, 
after  the  lead  process  with  the  cerebrosides  only,  to  one  of  which, 
kerasin,  it  has  a  slight  chemical  affinity.  This  might  explain  its 
absence  from  the  buttery  matter. 

Ejnsode  concerning  the  Shifting  of  Cadmium  Chloride  in  Mixtures 
of  Lecithin,  Parcimyelin,  and  Amidomyelin,  during  recrystcdlisation 
from  Spirit. — It  was  observed  that  precipitates  which  had  been 
exhausted  with  ether,  and  therefore  were  free  from  uncombined 
lecithin,  after  recrystallisation  from  spirit  left  some  free  lecithin 
in  the  mother-liquor,  which  could  be  precipitated  by  renewed 
addition  of  cadmium  chloride  solution.  It  had  also  been  observed 
that  such  preci^^itates  containing  amidomyelin  showed  a  higher 
percentage  of  cadmium  chloride  than  before.  Similar  data  were 
also  obtained  during  the  treatment  and  analyses  of  the  platinum 
salts.  On  the  basis  of  these  observations  the  following  hypothesis 
was  formed. 

Amidomyelin  probably  combines  with  cadmium  chloride  in  two 
proportions,  namely,  either  wdth  one  molecle  of  this  salt,  or  with 
two  molecles,  thus  : 

C,4H^,N.^P0iy  +  CdCl.^,  containing  17-90  per  cent.  CdCl^. 
C,^Hj,^^N,POi(>-f  2CdCl,,  containing  30-37  per  cent.  CdCU. 


The  former  has  a  tendency  to  saturate  itself  in  the  pi'esence  of 
lecithin  cadmium  chloride,  C42Hg^NP09  +  CdCl^,  containing  19 "42 
per  cent.  CdCl^,  and  during  recrystallisation  from  spirit,  or  during 
suspension  in  benzol  in  which  the  lecithin  salt  is  in  solution,  takes 
up  some  cadmium  chloride  from  a  portion  of  the  lecithin,  which 
is  thereby  set  free  and  remains  in  the  spirituous,  or  as  the  case 
may  be,  benzol  mother-liquor.  This  kind  of  shifting  of  the  cad- 
mium chloride  is  more  likely  to  occur  in  anhydrous  solvents,  or 
strong  spirit,  whereas  the  dissociation  under  the  influence  of  water, 
complete  during  the  process  of  dialysis,  is  partial,  particularly  in 
dilute  solvents  or  edulcorants. 

Continuation  of  the  Description  of  the  Process. — The  solutions  in 
cold  benzol  obtained  in  the  process  described  in  the  foregoing  are 
allowed  to  stand  for  some  days  in  the  cold  and  repeatedly  filtered. 
They  are  then  concentrated,  allowed  to  stand,  and  filtered  again, 
until  the  residual  solution  remains  quite  clear  and  free  from 
deposit.  Filtration  is  absolutely  required  to  prove  the  absence  of 
deposits,  as  these  are  so  transparent  that  they  easily  escape  from 
observation  by  the  eye. 

The  concentrated  thick  benzol  solution,  which  is  mostly  coloured 
and  strongly  fluorescent,  may  now  be  evaporated  to  dryness,  and 
the  residue  further  studied.  But  it  is  j)referable  to  add  to  it 
absolute  alcohol  as  long  as  a  precipitate  ensues.  Time  is  again 
wanted  to  complete  the  precipitation.  The  precipitate  is  washed 
with  alcohol,  dried  in  vacuo,  exhausted  with  ether,  and  recrys- 
tallised  from  spirit.  Now  a  portion  remains  insoluble  in  boiling 
spirit,  but  the  bulk  dissolves  and  is  deposited  on  cooling  as  a 
white  mass,  which,  under  the  microscope,  is  seen  to  consist  entirely 
of  needles  arranged  radially  in  stars  and  balls. 

Separation  of  Lecithin  from  Amiclomyelin  and  Paramyelin  ivhen  all 
are  in  the  free  state. — All  three  bodies  are  precipitated  by  cadmium 
chloride,  and  the  compounds  are  soluble  in  boiling  spirit.  When 
the  mixture  is  decomposed  in  one  way  or  another,  and  the  result- 
ing free  bodies  are  dissolved  in  hot  spirit,  the  amidomyelin  and 
paramyelin  separate  first  in  the  shape  of  white  leaflets,  again  on 
concentration  ;  from  the  highly  concentrated  spirit  a  mixture  of 
lecithin  and  little  amido-  or  paramyelin  is  at  last  deposited  as  an 
unctuous  mass.  When  this  is  treated  with  ether,  white  amido-  or 
paramyelin  remains  insoluble.  When  the  ether  solution  is  dis- 
tilled to  dryness  and  the  residue  treated  with  absohtfe  alcohol, 


lecithin  dissolves,  while  again  some  amido-  or  paramyelin  remains 
insoluble.  The  absolute  alcohol  solution  deposits  more  amido-  or 
paramyelin  on  long  standing,  particularly  at  low  temperatures. 
But  it  is,  perhaps,  not  practicable  to  obtain  perfectly  pure  lecithin 
without  a  trace  of  amido-  or  paramyelin  by  this  process,  although 
the  amido-  or  paramyelin  obtained  by  it  is  perfectly  free  from 
lecithin.  A  specimen  of  lecithin  thus  prepared  (by  dialysis,  etc., 
but  not  separated  as  CdCl2  salt  by  benzol)  gave  on  analysis  3-66 
per  cent,  P.  and  2*83  per  cent.  N.  The  amount  of  nitrogen 
shows  that  the  body  contained  yet  some  amidomyelin. 

The  lecithin,  when  thus  purified  as  far  as  j)Ossible,  gives  a  white 
CdCl2  salt  which  is  soluble  in  boiling  spirit,  and  when  deposited 
from  it  leaves  some  coloured  impurity  in  solution. 

On  the  mode  of  separating  lecithin  from  amidomyelin  by  benzol, 
when  both  bodies  are  combined  with  CdCl2,  see  ante^  and  in  the 
relative  paragraph  under  amidomyelin.  Paramyelin  can  be  sepa- 
rated to  some  extent  from  amidomyelin  by  the  greater  solubility 
of  its  hydrochlorate,  but  completely  only  by  the  solubility  of  its 
cadmium  chloride  compound  in  boiling  benzol,  in  which  amido- 
myelin is  insoluble. 

Properties  of  Lecithin. — Lecithin  is  a  white  crystalline  body, 
crystallising  in  thin  plates,  which  when  compressed  form  a  wax- 
like mass.  It  is  very  soluble  in  spirit,  being  only  deposited  when 
the  solution  is  extremely  concentrated.  A  slight  rise  in  the  tem- 
perature causes  the  crystals  to  redissolve.  When  to  its  cold 
'  saturated  solution  in  spirit  water  is  gradually  added  until  a  per- 
manent considerable  turbidity  is  produced,  and  when  this  turbidity 
is  cleared  up  by  heating,  the  solution  deposits  on  standing  lecithin 
in  the  semi  solid  hydrated  state.  The  solution  in  80  per  cent, 
spirit  treated  as  descril^ed  left  3*08  per  cent,  lecithin  on  evapora- 
tion. The  unctuous  lecithin  under  the  microscope  consists  of 
balls  in  concentric  layers.    Lecithin  is  easily  soluble  in  ether. 

It  is  easily  soluble  in  chloroform,  and  is  left  on  evaporation  as 
a  non-crystalline  mass. 

It  dissolves  in  oil  of  vitriol  with  a  yellow  colour,  and  on  addi- 
tion of  thick  cane-sugar  syrup  Easpail's  reaction,  a  purple  colour, 
is  gradually  produced,  changing  slowly  into  black.  The  reaction 
is  due  to  the  oleyl  radicle  contained  in  the  lecithin. 

Comjmmds  of  Lecithin. — An  alcoholic  solution  of  lecithin  is  pre- 
cipitated by  cadmium  chloride  ;  the  white  voluminous  precipitate. 


amorphous  at  first,  crystallising  on  standing  in  the  mother-liquor, 
is  easily  soluble  in  boiling  spirit,  and  dej^osited  on  rapid  cooling 
in  white  crystalline  granules  ;  on  slow  cooling,  acicular  crystals 
arranged  in  balls  and  rosettes  are  deposited.  They  are  very 
uniform  and  characteristic,  and  totally  different  from  sphingo- 
myelin cadmium  chloride.  This  precipitate  is  insoluble  in  cold 
and  boiling  ether,  easily  soluble  in  benzol. 

Platinum  Chloride  Hydrochlorate  of  Lecithin. — Lecithin  is  preci- 
pitated by  an  acidified  solution  of  platinum  chloride  in  spirit ; 
the  voluminous  yellow  precipitate  is  easily  soluble  in  ether,  and 
again  precipitated  from  this  solution  by  absolute  alcohol.  Its 
formula  is  2(C43Hg4NP08)-f-2HCl  +  PtCl4.  A  compound  also 
occurs  with  one  HCl  only,  and  another  without  any  HCl,  and 
containing  PtCl^  only. 

Lecithin  is  not  precipitated  by  a  mixture  of  lead  acetate  and 

Solubility  of  Lecithin  CdCl.^  Salt  in  Spirit. — Ten  cc.  of  the  84  per 
cent,  spirit  solution  which  had  deposited  a  crystallised  salt,  on 
evaporation  left  0*0387  g.  solid  matter.  One  part  of  the  salt 
therefore  requires  258  parts  of  spirit  at  17°  C.  for  solution. 

Bearing  of  the  Lecithin  CdCl.^  Salt  with  Benzol. — When  tlie  crys- 
tallised salt  is  placed  in  pure  dry  benzol  it  swells  and  becomes 
transparent,  but  does  not  dissolve.  If  now  the  mixture  be  heated 
for  some  time,  the  salt  dissolves  without  residue,  and  the  clear 
colourless  solution  does  not  form  any  deposit  on  cooling  and 
standing.  This  j)henomenon  is  due  to  hydration  of  the  crystal- 
lised salt;  during  the  first  boiling  with  benzol  the  water  is 
evolved  and  passes  over  with  the  benzol  vapours  ;  when  clear 
benzol  passes  over,  all  salt  is  and  remains  in  solution. 

Lecithin  Hydrochlorate,  C^gHg^ISTPOg  +  HCl. — The  pure  white 
cadmium  chloride  compound  is  suspended  in  spirit,  and  the  mix- 
ture is  saturated  cold  with  hydrothion.  It  is  now  heated  in  a 
water-bath  to  boiling  while  the  current  of  the  sulphuretted  gas 
is  continued,  until  the  filtrate  is  no  longer  affected  by  it.  The 
decomposed  matter  is  thrown  on  a  filter  arranged  on  a  steam- 
jacket,  and  the  colourless  spirit  solution  of  lecithin  hydrochlorate 
is  separated  from  the  cadmium  sulphide.  The  solution  deposits 
the  hydrochlorate  as  a  felted  mass  of  crystals.  By  slow  crystal- 
lisation from  dilute  solutions  white  crystals  are  obtained.  As  the 
cadmium  chloride  yields  two  molecles  of  hydrochloric  acid,  of 


which  only  one  combines  with  the  lecithin,  the  mother-liquor  con- 
tains free  acid  in  solution.  As  this  acid  decomposes  lecithin  at 
high  temperatures,  it  is  not  advisable  to  endeavour  to  obtain  the 
lecithin  hydrochlorate  which  remains  in  solution  in  the  spirit  by 
evaporation  of  the  latter  by  heat.  It  is  preferable  to  extract  all 
hydrochloric  acid  from  the  solution  by  mercuramin,  reprecipitate 
the  lecithin  by  cadmium  chloride,  and  redecompose  this  by 
hydrothion  in  a  minimum  of  spirit.  If  it  is  desired  to  obtain  the 
whole  amount  of  lecithin  in  a  given  preparation  as  hydrochlorate, 
the  body  should  be  neutralised  with  the  acid,  and  the  solution 
evaporated  in  a  vacuum  over  lime  and  oil  of  vitriol. 

The  hydrochlorate  crystallises  in  thin  leaflets,  to  be  seen  by  the 
microscope ;  they  are  hexagonal,  frequently  saucer-shaped,  and, 
owing  to  their  extreme  tenuity,  mostly  so  distorted  and  crumpled 
up  that  they  appear  as  a  confused  mass  of  curved  needles. 

{Human)  Lecithin  Hydrochlorate. — By  CdCl2  from  alcoholic  solu- 
tion of  white  matter  and  buttery.  Passed  through  benzol  process; 
the  soluble  in  the  cold  part  again  recrystallised  from  spirit.  The 
white  salt  was  decomposed  by  hydrothion,  the  solution  allowed 
to  crystallise  ;  the  crystallised  mass  was  recrystallised.  Dried  in 
vacuo  to  a  perfectly  white  mass  which  could  be  powdered  easily. 
At  98°  it  became  a  little  soft,  and  by  prolonged  heating  somewhat 
coloured.  It  gave  on  analysis  4*84  per  cent.  HCl,  2-03  per  cent.  X, 
and  4-29  per  cent.  P  ;  therefore,  HCl :  N  :  P  =  1  : 1  : 1. 

(Ox)  Lecithin  Cadmium  Chloride. 


Per  cents. 


43  C 



84  H 



1  N 



1-34  — 

1  P 



—  3-2i 

8  0 


1  Cd 



2  CI 







Cd  CL, 




C.^Hg.NPO.-fCdClo,  At.  W.  =  942,  requires  19-42  per  cent,  CdCl^. 



Chemolysis  of  Lecithin. — Lecithin,  when  isolated  as  platinic 
chloride  hydrochlorate  salt,  immediately  after  isolation  begins  to 
decompose,  and  completes  this  decomposition  during  the  steps 
necessary  for  its  purification.  Its  platinum  salt,  which  is  in  the 
first  instance  soluble  in  ether,  becomes  in  the  air  or  in  the  vacuum 
speedily  covered  with  oily  drops  (oleic  acid),  and  the  residual  salt 
is  then  insoluble  in  ether.  It  was  upon  such  changed  platinic  salt 
insoluble  in  ether  that  the  following  chemolysis  was  eff'ected : 

Water  alone  was  found  capable  of  removing  at  least  some  of 
the  platinic  chloride  ;  but  this  treatment  was  not  persisted  in,  and 
the  salt  was  boiled  with  two  molecles  of  BaH202  during  two  hours. 
The  decomposition  was  eff'ected  very  readily,  a  black  precipitate 
(of  platinum)  being  formed  simultaneously  and  insoluble  barium 
salts  of  certain  fatty  acids. 

The  Barium  Salts. — These  were  washed  with  water,  and  then 
decomposed  by  hydrochloric  acid,  in  the  presence  of  ether,  f  \  The 
ether  solution  was  distilled  to  dryness,  and  the  residual  matter 
converted  into  ammonium  soap ;  and  the  latter  in  its  turn  was 
converted  into  barium  salt  once  more,  and  after  drying  extracted 
with  much  boiling  absolute  alcohol.  The  alcoholic  extraction  was 
continued  to  perfection.  The  extracts  deposited  a  white  salt  on 
cooling,  which  was  isolated,  dried,  and  analysed;  it  gave  19-55 
j)er  cent.  Ba.  Oleate  of  barium  requires  19-59  per  cent.  Ba.  This 
salt  was  therefore  oleale  of  barium. 

The  barium  salt  left  undissolved  by  the  alcohol  was  insoluble 
in  ether.  It  was  once  more  decomposed  by  hydrochloric  acid  in 
the  presence  of  ether,  and  converted  first  into  ammonium  soap, 
and  again  into  barium  salt.  It  was  now  isolated,  dried  at  100°  C, 
and  analysed;  it  gave  19-82  per  cent.  Ba,  and  57-76  -per  cent.  C 
and  9-86  per  cent.  H. 

Computation  of  Analyses : 


4- At.  Wgts. 

Ba  =  l. 






9-86  ■ 











=  CJg^Hg^BaO^. 

This  was,  therefore,  apparently  margarate  of  harium. 
The  Barita  Solution. — The  excess  of  barita  was  first  removed 
from  the  solution  by  means  of  carbonic  acid,  and  then  nitric  acid 



was  added  to  strong  acidity.  In  this  state  the  solution  was  pre- 
cipitated by  phosphomolybdic  acid,  and  the  filtrate  reserved.  The 
precipitate  was  decomposed  by  hot  barita  and  concentrated  to  a 
low  bulk.  The  barium  which  still  remained  in  combination  with 
the  base  was  carefully  removed  by  the  exact  amount  of  sulphuric 
acid  necessary,  and  after  concentration  the  resulting  solution  was 
neutralised  by  HCl  and  precipitated  by  alcoholic  PtCl^.  The 
platinic  compound  crystallised  from  water  in  long  prismatic 

The  quantity  of  the  platinum  salt  obtained  was  very  near  to 
that  which  should  have  been  obtained  if  all  the  nitrogen  had 
existed  in  one  form  in  lecithin,  and  had  been  obtained  in  one 

Computation  of  Analyses: 


-^-At.  Wgts. 


























=  {C5H13NO),  (HCl),  PtCl,. 

The  filtrate  separated  from  the  phosphomolybdic  acid  precipi- 
tate of  the  base  was  found  to  contain  glycerophosphoric  acid. 
The  chemolysis  of  lecithin,  therefore,  is  complete,  as  there  were 
obtained : 

Oleic  acid  -       -       -  =  C^gH^^ 
Margaric  acid    -       -  ^C^-H.^^  0, 
Glycerophosphoric  acid  =  C3  Hg  PO^^ 
J^eurin     -       -       -  =C,  H^^N  O 

Total-       -       -  =C43H9oNPOii 

Deduct      -       -  -  O3  entered  in  chemolysis 

Leaves      -       -  =  C^^.^H^^NPOg  =  lecithin. 

I  have  lately  chemolysed  a  specimen  of  lecithin  which  had 
been  as  CdCl,  salt  entirely  soluble  in  cold  benzol,  and  had  been 
crystallised  from  spirit,  after  several  earlier  crystallisations  had 
been  removed.  It  yielded  oleic  acid,  margaric  acid,  glycerophos- 
phoric acid,  and  neurin.  In  the  course  of  this  chemolysis  I 
observed  that  benzol  is  a  better  medium  than  ether  for  separating 


the  lead  oleate  from  the  lead  margarate.  This  lead  process  also 
yields  a  purer  margarate  than  the  exhaustion  with  alcohol  adopted 
above ;  but  the  oleate  is  again  less  pure  than  that  deposited  from 

Note  on  Oleic  Acid  and  its  Reaction  tvith  Oil  of  Vitriol  and  Sugar. — 
Oleic  acid  is  generally  considered  to  have  much  affinity  for  oxigen, 
so  as  greatly  to  impede  attempts  to  obtain  it  in  a  pure  state. 
This  absorption  of  oxigen  is  considered  and  stated  to  be  attended 
with  the  production  of  a  brown  colour,  and  a  change  in  the  nature 
and  properties  of  the  acid. 

Pure  oleic  acid,  prepared  expressly  from  oil  of  almonds,  with 
the  view  of  comparing  it  with  the  oleic  acid  furnished  by  lecithin, 
showed  none  of  these  properties.  The  potassium,  ammonium, 
lead,  and  barium  salts  were  all  white,  and  showed  no  tendency  to 
become  coloured  on  exposure.  The  free  acid  was  also  free  from 
this  tendency,  and  was  only  very  faintly  yellow,  while  its  solution 
in  ether  was  colourless  and  did  not  become  brown  on  exposure. 
To  prove  the  purity  of  the  body  the  barium  salt  was  analysed  for 
barium,  and  found  to  contain  19"73  per  cent,  as  against  19  "60  per 
cent,  required  by  theory. 

Sulphuric  acid  turned  oleic  acid  yellowish  and  red,  but  chloro- 
form had  no  action  on  the  mixture.  It  gave  a  solution  with  acetic 
acid  which  was  so  turbid  that  no  spectrum  could  be  obtained. 

But  with  sulphuric  acid  and  sugar  it  immediately  turned 
purple  (with  sulphuric  acid  alone  it  was  yellowish-brown),  and  the 
product  dissolved  with  a  splendid  purple  colour  in  acetic  acid  ; 
the  solution  presented  the  following  spectrum  : 

In  the  concentrated  state  it  passed  red  at  A,  thence  a  shade 
increased  to  D,  then  black.  A  more  diluted  solution  presented 
one  broad  absorption  band  between  D  and  E.    End  at  G. 

The  edges  of  this  band  shaded  off  so  very  gradually  that  it  was 
difficult  to  fix  the  margins ;  this  solution  was  red,  but  presented 
a  green  fluorescence  ;  it  was  not  brilliant,  and  became  more  turbid 
on  standing. 

Oleic  acid  in  chloroform  was  now  mixed  with  a  drop  of  sugar 
syrup,  and  then  with  sulphuric  acid ;  it  immediately  became  in- 
tensely yellow ;  on  stirring  and  breathing  upon  it,  it  became 
purple,  but  the  colour  was  very  dark  and  mixed  with  brown. 

It  was  soluble  in  glacial  acetic  acid,  giving  the  above  spectrum. 
Chloroform  extracted  a  splendidly  purple  matter,  leaving  a  dingy 



one  behind.  This  sokition,  suitably  dihited  and  kept  anhydrous 
by  sulphuric  acid,  passed  red  to  C.  Further  diluted,  there  was  a 
band  between  C  and  D,  and  another  between  D  and  G  ;  blue  to  C. 

Again  diluted,  band  1  disappeared  and  band  2  contracted. 
Acetic  acid  solution  of  same  test  gave  same  band.  The  band 
became  shaded  off  near  green.  Therefore  with  chloroform  it 
presented  the  same  spectrum  as  phrenosin  and  kerasin,  but  these 
were  insoluble  in  acetic  acid,  in  which  the  oleic  acid  test  was  soluble. 

Theory  of  Lecithins  considered  as  Phosphatides. 



OP  4 



f  C*'i8^^3302  1 

]  C3H.O3 




^18^35^2  L  =n    H  IVPO 


























408  1 














The  first  three  radicles  in  each  formula  replace  a  molecle  of 
hydroxyl  each ;  but  the  addition  of  neurin  takes  place  under  cir- 
cumstances which  engender  the  expulsion  of  a  molecle  of  water 
from  the  neurin  itself.  The  mobility  of  this  molecle  of  water  in 
neurin  is  clearly  shown  in  the  course  of  the  synthesis  of  this  base. 

2.  Kephalins. 
a.  Kephalin. 

Purification. — The  crude  kephalin  obtained  by  the  primary 
operations  is  dried  under  the  air-pump  over  sulphuric  acid.  It 


must  be  repeatedly  taken  out  and  flattened  out  in  a  mortar,  and 
iigain  dried  before  it  becomes  dry  and  brittle,  and  can  be 
powdered.  Resolution  in  absolute  ether,  reprecipitation  by 
absolute  alcohol,  and  redrying  causes  a  great  improvement,  but 
also  much  loss. 

The  dry  substance  is  then  dissolved  in  pure  water,  10  g.  in 
the  litre,  and  after  complete  disintegration  by  agitation  in  a 
stoppered  bottle,  is  allowed  to  deposit  less  soluble  salts  and  im- 
purities, decanted  or  siphoned  from  these,  and  then  filtered  by 
2:>ressure  as  described. 

The  filtered  solution  is  now  treated  with  enough  hydrochloric 
acid  to  effect  complete  precipitation  of  all  kephalin  as  hydro- 
chlorate,  a  salt  which  appears  in  voluminous  flakes,  and  on 
shaking  collects  on  the  surface  of  the  liquid.  (This  precipitation, 
like  others  to  be  related,  affords  a  good  criterion  of  the  previously 
dissolved  state  of  the  substance.)  The  mother-liquor  is  drawn 
from  underneath  the  precipitate  with  a  siphon  ;  fresh  water  is 
poured  on  the  precipitate,  and  the  whole  is  now  placed  upon  a 
paper  filter  or  cloth,  and  washed  Avith  water  until  it  begins  to  swell 
and  dissolve.  At  that  point  it  is  found  that  all  HCl  is  washed  out, 
and  that  only  pure  liydrated  keijlialin  remains  on  the  filter.  This 
was  expressly  proved  by  analysis  in  several  cases,  but  more 
especially  in  the  following  experiment. 

Expulsion  of  Eydrochloric  Acid  from  Kephalin  by  Water. — Half  a 
litre  of  a  weak  kephalin  solution  was  precipitated  by  HCl  and 
filtered  ;  the  precipitate  on  filter  was  placed  in  500  cc.  of  water  to 
test  its  solubility,  and  was  found  insoluble,  but  the  water  con- 
tained free  HCl.  It  was  again  filtered,  and  after  the  solution  had 
run  through  absolute  alcohol  was  blown  on  the  precipitate ;  this 
became  adhesive,  and  the  solution  refused  to  filter.  The  alcohol 
and  precipitate  were  transferred  to  a  beaker,  and  the  whole  was 
gently  warmed  in  a  water-bath  to  a  temperature  not  much  above 
60°.  The  precipitate  fused,  but  dissolved  very  sparingly, 
apparently  the  less  the  more  the  alcohol  made  the  precipitate 
anhydrous.  The  alcoholic  solution  was  now  filtered  off  warm, 
and  the  undissolved  portion  of  the  precipitate  taken  up  with 
ether.  The  solution  so  obtained  was  of  a  colour  resembling 
ordinary  kephahn  in  ether,  and  was  poured  into  the  alcoholic 
solution.  The  precipitate  which  ensued  was  fawn-coloured, 
adhesive,  and  leathery  ;  it  was  isolated,  washed  with  absolute 


alcohol,  the  mother-liquor  being  squeezed  out  of  it,  then  pressed 
and  dried  in  air-pump.  The  whole  was  analysed  for  chlorine  as 
follows.  It  was  heated  to  dryness  in  a  strong  solution  of  pure 
soda,  with  carbonate  and  nitre  added,  and  the  mass  was  burned. 
The  fused  mass  was  dissolved  in  dilute  nitric  acid,  and  the  solu- 
tion tested  with  silver  nitrate.  No  ^precipitate  occurred, 
showing  that  ili  e  body  ohtained  in  this  process  is  not  a  hydrochlovate, 
but  kephalin  in  a  j^urified  state. 

Bases  and  Salts  wJdch  are  in  combination  tvith  Kephcdin  after  Filtra- 
tion of  its  Aqueous  Solution. — The  solution  of  hydrochloric  acid  and 
other  matters  filtered  from  the  precipitated  kephalin  was  evaporated 
to  dryness.  A  portion  was  then  boiled  with  solution  of  barita, 
when  traces  of  ammonia  were  evolved.  The  rest  of  the  residue 
was  then  ignited  in  a  platinum  dish  to  destroy  all  traces  of 
organic  matter.  The  ash  was  slightly  molten,  and  only  partially 
soluble  in  water,  but  easily  soluble  in  water  slightly  acidified  with 
hydrochloric  acid.  The  solution  was  filtered  from  a  trace  of 
carbon,  and  treated  with  excess  of  ammonia,  whereupon  an  abun- 
dant i)recipitate  of  earthy  salts  fell  down,  and  the  solution  assumed 
a  deep  blue  colour.  Precipitate  and  solution  were  separated  l)y  filtra- 
tion. The  precipitate  dissolved  readily  in  a  little  HCl,  forming 
a  slightly  red  solution,  indicating  presence  of  iron,  which  was  con- 
firmed by  the  sulphocyanide  test.  In  another  portion  of  the 
solution  dilute  sulphuric  acid  gave  an  abundant  precipitate  of 
gypsum,  showing  presence  of  ccdciuui.  In  another  portion  the 
molybdate  test  showed  the  presence  of  p'^^osphoric  acid.  To  the 
remaining  portion  a  few  drops  of  ferric  chloride  were  added,  then 
sodic  carbonate  nearly  to  neutrality,  and  lastly,  excess  of  baritic 
carbonate.  This  mixture  was  allowed  to  stand,  filtered,  and  the 
filtrate,  freed  from  excess  of  barita  by  sulphuric  acid,  was  again 
filtered.  The  filtrate,  after  supersaturation  with  ammonia,  gave 
a  great  precipitate  with  ammonium  oxalate,  insoluble  in  acetic 
acid,  showing  presence  of  much  calcium.  The  filtrate  from  this 
calcic  oxalate  on  concentration  and  treatment  with  ammonia, 
ammonium  chloride,  and  sodium  phosphate,  gave  the  j^recii^itate 
characteristic  of  magnesium.  The  precipitate  produced  by  barium 
carbonate  was  boiled  with  excess  of  pure  soda,  and  the  filtrate 
warmed  with  ammonium  chloride,  when  only  a  turbidity  was 
produced,  indicating  the  absence  of  aluminium. 

The  alkaline  filtrate  from  the  foregoing  precipitate  by  ammonia 


was  tested  for  lime  by  oxalate,  when  a  considerable  precipitate 
was  produced,  showing  the  presence  of  lime  tmcombined  with  jjJws- 
pJioric  acid,  and  which  must  therefore  have  been  in  combination 
with  part  of  the  kephalin.  The  blue  solution  was  again  filtered 
from  calcium  oxalate,  which  had  been  entirely  precipitated,  and 
acidified  with  hydrochloric  acid.  The  copper  was  precipitated  by 
hydro thion,  the  filtrate  evaporated  to  dryness,  ignited,  and  the 
residue  tested  for  alkalies.  This  residue  was  considerable,  sur- 
mounting in  quantity  or  bulk  the  bases  previously  removed.  It 
was  fusible  with  ease,  and  on  solidification  became  white  and 
crystalline,  but  interspersed  with  many  red  particles  of  ferric 
oxide.  The  fusion  showed  it  to  be  mainly  potassium  chloride,  but 
there  was  also  some  sodium  chloride  present,  as  indicated  by  the 
flame  reaction,  and  the  ferric  oxide  which  had  escaped  precipita- 
tion by  excess  of  ammonia. 

It  is  therefore  proved  that  the  kephalin  obtained  by  the  alcohol 
and  ether  processes,  and  purification  by  solution  in  water  and 
filtration,  consists  of  kephalin  in  the  free  state ;  and  of  kephalin 
combined  with  ammonium,  sodium,  potassium,  calcium,  iron, 
copper,  and  with  calcium  and  magnesium  phosphates. 

This  experience  was  repeated  a  great  number  of  times  on,  in 
the  aggregate,  several  hundred  grammes  of  dry  kephalin  ;  the 
calcium  and  potassium  salts  were  always  found  prevailing  greatly 
in  quantity  over  the  others  ;  none  were  ever  absent.  Although 
I  have  not  compared  the  total  of  the  neutralising  power  of  the 
bases  with  the  total  of  the  acid-combining  power  of  the  kephalin, 
by  direct  quantitative  experiment,  I  am  sure  that  much  kephalin 
must  have  been  present  in  the  free  state,  as  will  appear  from 
future  developments  concerning  the  combining  and  dissociating 
powers  of  this  body. 

Dialysis  of  Kephalin. — A  solution  of  5  g.  of  crude  kephalin  v/as 
dissolved  in  500  cc.  of  water,  and  formed  a  white  thick  liquid, 
from  which  some  cholesterin  crystallised  on  standing.  It  was 
then  placed  on  a  dialyser  of  parchment  paper.  A  trace  of 
kephalin  passed  into  the  water,  but  so  small  was  the  quantity 
that  no  chemical  operation  could  be  undertaken  with  it. 

Kephalin  does,  practically,  not  dialyse,  but  acts  as  a  colloid, 
and  allows  its  impurities  to  pass  out  into  the  water. 

Clarification  and  Decolonisation  of  JFaterij  and  Ethereal  Solutions 
of  Kephalin. — To  a  solution  of  1  g.  kephalin  in  100  cc.  of  water, 


5  cc.  of  filtered  fresh  ivhHe  of  egg  were  added,  and  the  mixture 
was  heated  in  a  flask  in  the  water-bath  ;  it  remained  turbid,  and 
no  separation  of  coagulated  albumin  took  place.  The  mixture 
had  a  faintly  alkaline  reaction.  On  addition  of  a  drop  of  acetic 
acid  to  the  heated  mixture  a  copious  precipitate  ensued,  which 
enclosed  both  kephalin  and  albumen  (the  kephalin  solution  b}' 
itself,  cold,  is  only  partially  or  imperfectly  precipitated  by  the 
same  acetic  acid).  By  filtration  a  perfectly  clear  liquid  was 
obtained,  which  was  no  longer  precipitated  by  barita  water  or 
platinic  chloride,  and  not  changed  by  boiling.  Consequently,  all 
albumen  and  all  kephalin  were  removed  together  from  the  solu- 
tion, and  perhaps  in  part  combined.  Cold  absolute  alcohol  in 
large  quantity  extracted  all  or  nearly  all  kephalin  from  the  albu- 
men, and  on  distillation  left  it  ijerfedly  u-Mte.  The  albumen,  on 
the  other  hand,  was,  after  washing  with  alcohol  and  ether,  in  a 
finely  divided  pulverulent  state,  and  not  hard  nor  horny.  This 
process  is  therefore  useful  for  preparing  snow-white  kephalin, 
which  must,  however,  not  again  be  brought  into  contact  with 
ether,  as  that  would  immediately  cause  it  to  become  coloured 
under  the  influence  of  oxidation, 

Ivfiuence  of  Animal  Charcoal  on  Water  Solution  of  Kejjhalin. — 
To  a  solution  of  1  g.  kephalin  in  100  cc.  of  water,  2  g.  of  pure 
animal  charcoal  were  added,  the  mixture  shaken,  and  then  sub- 
jected to  the  vacuum  filter.  A  little  fluid  passed,  which  became 
at  last  quite  clear.  A  portion  of  the  last  clearest,  collected  by 
itself  and  tested,  was  found  to  be  almost  pure  water  ;  for  hydro- 
chloric acid,  platinic  chloride,  barita  hydrate,  and  lead  acetate, 
l^roduced  the  very  feeblest  precipitates  only,  while  the  original 
solution  was  made  solid  by  the  same  precipitants.  The  animal 
charcoal  therefore  retained  the  kephalin,  and  when  isolated  and 
extracted  with  alcohol  yielded  it  up  to  that  solvent.  This  ex- 
perience, as  well  as  that  made  with  albumen,  shows  that  the 
watery  solution  of  kephalin  cannot  be  clarified  by  these  agents,  if 
indeed  they  do  not  show  also  that  the  condition  of  kephalin  is 
one  of  suspension  and  not  of  true  solution.  That,  however, 
charcoal  has  a  special  attraction  for  kej^halin,  such  as  it  also 
exhibits  towards  other  ammonium  ])ases  and  alkaloids  of  un- 
doubted solubility  in  water,  is  shown  by  the  following  experiment. 

Bearing  of  Kephalin  in  Ether  tcith  Charcoal— A  concentrated 
solution  of  kephalin  in  ether  was  treated  with  much  animal  char- 


coal,  in  order  to  be  decolorised.  The  object  was  but  partially 
obtained.  The  charcoal,  after  filtration  and  washing,  was  found 
to  retain  much  kephalin,  which  was  extracted  by  boiling  absolute 
alcohol,  and  from  this  deposited  on  cooling  in  a  perfectly  white 
state.  The  solution  deposited  more  on  spontaneous  evaporation. 
Both  were  tested  and  identified  as  kephalin. 

Kephalin  therefore  can  be  removed  from  watery  solution  by 
charcoal  and  curdling  albumen,  and  again  extracted  from  these 
substances  by  hot  or  cold  alcohol  in  large  quantity,  and  obtained 
from  these  solutions  in  a  perfectly  white  state. 

Ultimate  Analysis  of  Kej^halin. — A  specimen  of  highly  purified 
kephalin  was  passed  through  the  water-filtration  and  hydrochloric 
acid  process  ;  it  amounted  to  four  litres  of  one  per  cent,  solution, 
and  after  resolution  in  ether  and  precipitation  by  alcohol,  left 
about  30  g.  dry  matter.  It  was  thoroughly  dried  in  vacuo  over 
sulphuric  acid,  being  frequently  triturated,  and  ultimately  reduced 
to  a  fine  powder.  Carbon  and  hydrogen  were  determined  by 
combustion  with  lead  chromate  and  copper  turnings.  Nitrogen 
was  determined  by  volume,  the  bichromate  and  carbonate  mixture 
being  used  for  production  of  carbonic  acid  gas.  Phosphorus  was 
determined  by  evaporating  the  substance  with  solution  of  pure 
soda,  made  from  metallic  sodium,  mixed  with  carbonate  and 
nitre,  to  dryness,  slowly  deflagrating,  etc.,  and  determining  phos- 
phoric acid  by  magnesia  method. 

Thus  were  obtained  the  following  percentages  and  atoms  : 



~  by  At.  Wgt. 

~  by  N  =  l 


Per  cents. 

C  60-00 



42  C 



H  9-39 



79  H 



N  1-68 






P  4-27 






0  24-66 



13  0 




leading  to  formula  C^^H.^NPO^^  =  C^.^H^gNPOg  +  5Bfi. 

We  shall  see  hereafter  that  this  formula  is  supported  by  the 
results  of  the  analysis  of  a  number  of  other  preparations,  being 
partial  or  complete  compounds  of  kephalin,  of  which  the  organic 
matter  always  has  the  composition  of  the  free  substance  ;  the 
results  of  a  series  of  chemolytic  experiments  lead  to  the  latter 
formula.    But  the  assumption  of  the  presence  of  five  molecles  of 


water  of  hydration  brings  the  constituent  hydrogen  to  so  low  a 
figure  that  it  cannot  be  explained  out  of  the  sum  of  the  chemolytic 
products.  On  the  other  hand,  the  assumption  of  the  presence  of 
five  atoms  of  loosely  attached  oxygen  meets  also  with  theoretical 
objections.  The  difficulty  here  touched  requires  evidently  ex- 
perimental elucidation. 

SolubUUIes  of  Kephalui. — In  water  kephalin  swells  and  forms  an 
emulsion,  ultimately  an  imperfect  turbid  solution.  Its  affinity 
for  water  is  very  great,  and  the  List  quantity  of  water  is  expelled 
from  it  in  the  vacuum  only  with  great  difficulty  and  after  a  long 
time.  From  a  watery  solution  or  mixture  it  cannot  be  extracted 
by  ether,  as  the  liquids  form  an  emulsion  which  persists  even  after 
a  portion  of  the  ether  has  separated  from  the  water.  This  emul- 
sion is  very  thick,  like  paste,  white  like  milky  water,  and  practi- 
cally unmanageable.  When  a  drop  or  a  few  drops  of  a  concentrated 
ether  solution  are  allowed  to  fall  into  a  test-tube  full  of  water,  the 
mixture  is  at  once  transformed  into  a  white  jelly,  which  is  so  firm 
that  the  tube  can  be  turned  upside  down  without  anything  flowing- 
out  of  it.  Solutions  of  kephalin  in  water  on  standing  do  nob 
decompose  or  become  mouldy,  even  in  the  course  of  some  weeks. 

Cold  absolute  alcohol  dissolves  a  little  kephalin,  more  on  boiling, 
and  deposits  a  part  on  cooling  in  white  flocks.  One  hundred 
parts  absolute  alcohol  at  17°  C.  dissolve  seven  parts  ke^^halin ;  at 
boiling  heat  of  the  alcohol  nine  parts,  of  which  two  parts  are 
deposited  on  cooling.  AVhen  an  excess  of  kephalin  is  boiled  with 
an  insufficient  amount  of  alcohol,  the  j^art  which  remains  insolul)le 
does  not  seem  to  undergo  any  change,  for  it  retains  its  solubility 
in  ether  and  precipitability  by  alcohol  and  other  reactions. 

In  ether  kephalin,  when  not  too  much  hydrated,  is  highly 
soluble  ;  when  dry  it  is  soluble  in  anhydrous  ether  in  almost  any 
proportions  ;  it  does  not  crystallise  from  this  solution,  and  cannot 
be  made  to  deposit  as  from  a  mother-liquor.  It  is  precipitated 
from  the  ether  solution  by  an  equal  or  greater  volume  of  alcohol 
in  white  clouds,  which  combine  to  clots,  and  ultimately  forms  a 
firm  substance,  which  becomes  at  first  plastic,  and  then  dries  in 
vacuo  to  a  hard  brittle  mass.  The  ether  solution  becomes  quickly 
red  in  transmitted  light,  and  fluoresces  with  a  fine  green  colour. 
No  other  phosphorised  or  other  brain  ingredient  shows  this  pecu- 
liarity except  kephaloidin. 

A  specimen,  tln-icc  precipitated  from  ether  by  alcohol,  and 


when  last  in  ether,  exposed  during  twenty-four  hours  in  ice  to  a 
temperature  of  0°,  proved  soluble  in  cold  benzol,  and  very  soluble 
in  hot.  It  formed  a  yellow  solution.  A  sample  in  a  test-tube 
exposed  to  frost  gave  no  deposit.  The  addition  of  alcohol  to  the 
benzol  solution  produced  a  slight  precipitate,  insoluble  in  excess 
of  alcohol,  but  soluble  in  excess  of  benzol,  and  soluble  on  heating. 
Benzol  can  therefore  not  be  used,  like  ether,  for  the  purification 
of  kephalin. 

Reactions  of  the  Aqueous  Solution  of  Keijhalin. — 1  per  cent, 
solution,  filtered  by  air-pressure  through  three-fold  Swedish  filter- 
paper,  was  used. 

1.  Hydrochloric  acid  gives  a  bulky  curdy  precipitate,  slightly 

yellow,  and  after  isolation  soluble  in  ether,  not  precipi- 
tated b}^  alcohol  from  its  ethereal  solution.  (In  the 
filtrate  from  this  hydrochloric  acid  precipitate  platinic 
chloride  produces  the  merest  opacity.)  But  from  the 
ethereal  solution  of  the  HCl  precipitate  alcoholic  PtCl_,^ 
throws  down  a  precipitate,  which  is  soluble  in  ether, 
and  reprecipitated  by  alcohol. 

2.  Sulphuric  acid  produces  a  precipitate  like  that  produced 

by  HCL 

3.  Nitric  acid  the  same  as  the  previous  acids. 

4.  Barita  water  produces  a  bulky  curdy  precipitate. 

5.  Lime-water  produces  a  similar  precipitate,  but  it  does  not 

separate  like  the  BaH^O^  precipitate. 

6.  Cadmic  chloride  induces  a  curdy  precipitate  which  readily 


7.  Zinc  chloride  behaves  similar  to  CdCl.,. 

8.  Mercuric  nitrate  produces  a  dense  precipitate,  which  is  in- 

soluble in  nitric  acid,  but  coloured  slightly  yellow 
thereby,  heat  being  evolved.  The  precipitate  is  some- 
times rose-red,  and  in  adhesive  flakes.  Washed  and 
allowed  to  stand  with  water  it  becomes  again  white, 
ropy,  and  adhesive,  and  soft,  and  on  being  shaken  easily 
dissolves  in  water  in  the  manner  of  the  original  kepha- 
lin. The  mercuric  nitrate  seems  therefore  to  be  separated 
by  water  from  kephalin  in  the  same  manner  as  other 
salts  and  acids  are. 

9.  Barium  chloride  produces  a  good  dense  flaky  precipitate. 

Immediately  after  isolation  it  is  insoluble  in  water,  in- 
soluble in  alcohol,  but  easily  soluble  in  ether,  and 
apparently  reprecipitated  by  alcohol.  This  reprecipitated 
matter  contains  barium,  but  gives  it  up  again  to  water. 

10.  Calcium  chloride  acts  like  BaCl.^. 

11.  Platinic  chloride  produces  a  bulky  precipitate. 


12.  Ammonia  makes  solution  a  little  turbid,  but  causes  no  pre- 


13.  Platinic  chloride  mixed  with  HCl  produces  a  very  well- 

defined  precipitate. 

14.  Magnesium  chloride  causes  a  very  precise  immediate  preci- 


15.  Ferric  chloride  produces  a  yellowish  turbidity  and  imperfect 


16.  Uranic  nitrate  produces  a  white  turbidity  and  imperfect 


1 7.  Watery  bromine  produces  a  bulky,  nearly  white  precipitate, 

soluble  in  caustic  potash  ;  acetic  acid  added  to  this  again 
liberates  the  precipitate.  Chloroform  added  to  this  mix- 
ture produces  a  chloroform  solution  of  Br  at  the  bottom, 
containing  the  excess  of  reagent,  and  an  impracticable 
white  emulsion  on  the  top. 

18.  Cupric  nitrate  "J 

19.  Cupric  chloride  f   All  produce  perfect  precipitates  of  a 

20.  Cupric  sulphate  (       greenish-white  colour. 

21.  Cupric  acetate  ) 

22.  Mercuric  chloride  makes  the  solution  very  turbid,  but  pro- 

duces no  precipitate. 

23.  Mercuric  acetate  causes  an  immediate  complete  precipitate. 

24.  Silver  nitrate,  immediate  complete  precipitate,  darkening  a 

little  when  exposed  to  sunlight. 

25.  Gold  terchloride,  and  a  drop  of  hydrochloric  acid,  cause 

an  immediate  precipitate,  which  blackens  over  night. 

26.  Antimonic  chloride  produces  a  very  bulky  precise  white 


27.  Stannous  chloride,  a  white  flaky  complete  precipitate. 

28.  Stannic  chloride,  a  precipitate  and  turbid  solution. 

29.  Tannin  in  water,  no  particular  reaction. 

30.  Picric  acid,  a  turbidity,  but  no  manageable  precipitate. 

31.  Arsenious  acid,  a  precipitate  and  turbidity. 

32.  Arsenic  acid,  a  very  complete  immediate  precipitate. 

33.  Phosphoric  acid,  a  very  complete  immediate  precipitate. 

34.  Basic  lead  acetate,  a  precipitate  and  very  turbid  solution ; 

no  perfect  separation. 

In  none  of  the  foregoing  reactions  was  any  artificial  heat  em- 
ployed, but  they  were  all  made  at  the  ordinary  temperature. 

It  was  found  that  most  of  these  precipitates  could  not  be 
washed  with  water  without  losing  either  acid  or  base,  or  salt, 
with  which  they  were  combined.  But  most  of  them  remained  in- 
soluble in  water  until  the  point  of  i)urity  was  reached,  when  the 
kephalin  either  dissolved  in  the  pure  water,  or  clogged  the 


Compounds  of  Kephalin, 

Kephalin  Cadmium  Chloride. — Two  litres  of  a  filtered  1  per  cent, 
solution  were  precipitated  by  dilute  HCl.  The  mother-liquor  was 
drawn  off,  and  the  precipitate  washed  by  agitation  with  water. 
The  washing-water  was  again  drawn  off,  and  watery  solution  of 
cadmium  chloride  added,  which  caused  great  condensation  of  the 
precipitate.  The  liquor  was  again  drawn  off,  and  the  precipitate 
shaken  violently  with  a  great  quantity  of  alcohol  containing 
alcoholic  cadmium  chloride.  Thus  the  precipitate  was  condensed 
to  a  viscous  mass,  from  which  the  mother-liquor  was  drawn  off, 
and  the  alcohol  entirely  removed  by  careful  manipulation.  After 
draining,  the  precipitate  was  dissolved  in  ether,  and  to  the  ethereal 
solution  was  added  alcoholic  cadmium  chloride  cautiously,  till  a 
slight  permanent  precipitate  was  perceived.  This  was  removed 
by  filtration,  and  the  brilliant  fluorescent  filtrate  precipitated  by 
absolute  alcohol.  The  viscous  mass  was  again  drained  from  all 
alcohol  by  pressure  with  a  glass  rod.  Kedissolved  in  ether,  it 
formed  a  perfectly  clear  solution,  which  was  reprecijntated  by 
absolute  alcohol,  when  the  compound  came  down  in  an  almost 
pulverulent  state.  It  was  thrown  on  a  filter,  washed  with  absolute 
alcohol,  then  removed  on  a  glass  dish  and  placed  under  a  dryer, 
then  in  a  vacuum  over  sulphuric  acid,  and  frequentl}^  removed  to 
be  powdered  in  a  mortar,  and  ultimately  finely  pulverised.  It 
was  then  subjected  to  elementary  analysis.  Carbon  and  hydrogen 
were  determined  by  combustion  with  PbCrO^,  and  copper  turnings. 
Nitrogen  was  determined  as  gas.  Chlorine,  cadmium,  and  phos- 
phorus were  determined  by  fusion  with  caustic  soda,  nitre,  and 
carbonate,  solution  of  salts  in  acid,  precipitation  of  cadmium  by 
hydrothion,  and  conversion  into  carbonate.  Chlorine  and  phos- 
phorus were  determined  in  filtrate  from  cadmic  sulphide  by  the 
usual  methods.  The  cadmium  and  chlorine  were  in  the  relation 
of  Cd :  CI2,  inasmuch  as  4*15  parts  chlorine  require  6-54:  parts 

Summary  of  per  cent,  found  : 



53-603  ] 
8-519  i 

1-37    \  89-38 

3-54:  I 
22-35  J 






Calculation  shows  that  the  kephalin  is  not  completely  saturated 
with  CdCl2;  that  about  four  parts  out  of  nine  are  uncombined. 
For  the  formula,  derived  from  the  organic  matter  with  P  as  1, 
i.e.,  Qj^^^^V0y^,Q^Q\.2  yields  the  equation — 

C42H^c,NPOi3,CdCl2  CdCl, 

1019  :    183     -     100  :  17-95, 

whereas  only  10*62  per  cent.  CdCl^  were  found. 

Deducting  CdCU,  and  calculating  per  cents,  of  elements  in 
organic  body,  we  get — 

-r-  by  At.  Wgts. 

-^  by  P  as  1. 

At.  Wgts 



























leading  to  formula  C^gH^gNPO^g,  with  an  atomic  weight  of  836, 
thus  fully  sustaining  the  composition  of  the  free  substance. 

As  10  parts  of  CdCl^,  supposed  to  be  combined  with  a  molecle 
of  kephalin,  correspond  to  59  parts  of  compound,  about  40  j^er 
cent,  of  the  above  substance  may  have  been  free  kephalin. 

The  very  weak  chemical  affinities  of  kephalin  are  here  exhibited 
in  a  striking  manner ;  CdCl2  was  brought  into  contact  with  it  at 
various  periods,  and  yet  could  not  be  retained  in  combination. 
This  is  due  to  the  circumstance  that  CdCl2  cannot  be  dissolved  in 
absolute,  but  only  in  somewhat  watery  alcohol ;  and  even  little 
water  decomposes  the  compound,  and  carries  the  CdCU  away,  as 
will  be  shown  by  special  experiment  hereafter. 

Kephalin  u'ith  Hydrochloric  Acid  and  Flatinic  Chloride. — About 
three  litres  of  1  per  cent,  solution,  which  by  the  deposition  of  the 
insoluble  part  and  filtration  had  lost  much  of  the  1  per  cent, 
originally  dissolved,  were  treated  with  a  mixture  of  HCl  and 
PtCl^  in  slight  excess.  A  bulky  yellowish-white  curdy  precipitate 
ensued,  and  rose  to  the  surface ;  it  was  allowed  to  contract,  and 
the  yellow  mother-liquor  drawn  from  beneath  it  by  a  siphon. 
Absolute  alcohol,  equal  in  bulk  to  the  precipitate,  was  now  2)0ured 
ui)on  it,  and  the  mixture  violently  shaken.  This  caused  a  further 
contraction  of  the  precipitate,  indicated  by  lesser  bulk,  increase  of 
the  yellow  colour,  and  production  of  adhesiveness.    The  alcoholic 


liquid  was  again  siphoned  off,  and  another  quantity  of  absohite 
alcohol  was  now  poured  on  the  precipitate,  and  the  mixture 
violently  shaken.  The  precipitate  thereby  became  deep  yellow, 
adhering  to  the  glass,  and  so  contracted  that  the  liquor  could  be 
poured  off  quite  clear.  The  precipitate  was  now  treated  with  a 
minimum  of  ether,  in  which  it  proved  quickly  and  entirely  soluble. 
On  filtration,  nothing  whatever  remained  on  the  filter.  An  equal 
volume  of  absolute  alcohol  was  added  to  the  ether  solution, 
whereby  almost  the  whole  of  the  salt  was  precipitated.  The 
latter  was  freed  from  mother-liquor  by  careful  manipulation  with 
a  glass  rod,  redissolved  in  absolute  ether,  which  gave  a  brilliant 
solution  requiring  no  filtration,  and  this  was  reprecipitated  by 
absolute  alcohol  in  equal  volume,  added  in  a  thin  stream  while 
the  liquid  was  being  stirred.  The  mother-liquor  was  poured  off ; 
the  precipitate,  which  immediately  became  brittle  and  hard  on 
contact  with  absolute  alcohol,  was  drained  from  alcohol  and  placed 
over  sulphuric  acid  in  the  vacuum. 

Another  amount  of  the  same  body  was  made  from  four  litres 
of  a  1  per  cent,  solution  in  the  same  way,  with  this  difference — 
that  whereas  in  the  first  case  the  precipitate  was  washed  with 
alcohol  directly,  in  this  case  two  washings  with  water  were  carried 
out  before  the  application  of  alcohol.  This  was  done  in  order  to 
test  the  effect  of  water  upon  the  compound  desired  to  be  pro- 
duced. It  was  found  that  the  dry  body  treated  with  ether  and 
alcohol  like  the  first  preparation  contained  only  a  trace  of  platinum 
and  a  '/estige  of  chlorine,  both  elements  being  too  small  in 
quantity  for  accurate  determination. 

Both  preparations  were  therefore  united,  and  it  was  sought  to 
combine  them  with  platinic  chloride  under  circumstances  where 
the  influence  of  water  was  as  much  as  possible  excluded.  (It 
must  be  remembered  that  solid  platinic  chloride  contains  six 
molecles  of  hydration  water,  which  it  necessarily  carries  into  all 
its  solutions.)  They  were  dissolved  in  ether,  and  an  ethereal 
solution  of  PtCl^  was  added,  then  precipitated  with  absolute 
alcohol ;  again  dissolved  in  ether,  and  treatment  with  PtCl^  re- 
peated. Ultimately  the  precipitate  was  dissolved  in  pure  ether, 
reprecipitated  by  pure  alcohol,  and  dried  in  vacuo. 

Analysis  gave  3-592  per  cent.  Pt,  and  3-265  per  cent.  CI.  If 
the  platinum  had  been  accompanied  by  only  as  much  chlorine  as 
corresponds  to  tetrachloride,  2-58  per  cent.  CI  should  have  been 


found.  By  calculation  we  find  that  there  is  one-fifth  of  CI  more 
than  corresj^onds  to  this  proportion,  viz.,  1  Pt:  5  01  =  3-592  Pt : 
3-22  CI. 

A  compound  of  the  presumable  formula  : 

2(C^^H^c,NPOi3)  +  2ClH  +  PtCl4  with  an  atomic  weight  of  2083 
requires  9-5  per  cent.  Pt  and  10-2  CI.  Consequently,  the  platinic 
chloride  compound  comprises  about  one-third  of  the  kephalin,  of 
which  two-thirds  are  uncombined. 

It  is  thus  seen  that  although  kephalin  is  most  completely  pre- 
cipitated by  PtCl^  from  its  watery  solution,  yet  by  the  process  of 
solution  and  precipitation  with  solvents  in  which  PtCl^  is  soluble 
most  of  the  PtCl4  is  extracted  from  the  combination  and  lost  in 
the  mother-liquors,  just  as  it  is  almost  entirely  extracted  from  the 
same  precipitate  by  water.  In  short,  the  acids,  bases,  and  metallic 
salts  which  easily  combine  with  kephalin  when  they  are  present 
in  excess,  are  rapidly  separated  from  it  by  solvents  in  which  they 
themselves  are  readily  soluble. 

Chemically  speaking,  these  results  are  disappointingly  negative, 
inasmuch  as  they  refuse  to  furnish  the  ordinary  means  for  deter- 
mining the  atomic  weight  and  for  finding  guarantees  of  purity  of 
preparations.  But  physiologically  these  features  are  of  the 
greatest  interest,  inasmuch  as  they  show  us  a  marvellous  diversity 
of  power  of  reaction  of  kephalin,  by  its  entering  into  and  out  of 
combination  according  to  external  circumstances.  When  the  com- 
binants  are  off"ered  in  a  concentrated  state  they  are  retained ; 
when  the  liquids  which  carry  the  combinants  (blood,  serum, 
cerebrospinal  fluid)  become  again  diluted,  the  combined  matters 
must  again  pass  into  solution  and  travel  further.  Thus  every 
change  of  chemical  composition  of  the  juices  of  the  body  must 
necessarily  and  powerfully  affect  the  condition  of  the  brain 
and  nerves,  and  of  all  tissues  and  cells  containing  their  specific 

h.  Amldohephalin. 

The  details  of  the  observation  regarding  this  principle,  and  of 
its  transformation  into  lead  salt,  Avill  be  given  lower  down,  in  the 
section  of  the  dinitrogenised  monophosphatides. 

c.  Oxilcephalin  with  Cadmium  Chloride^  C42H^c)NPOi4,CdCl2. 

When  the  white  matter  (Ox)  has  been  extracted  with  ether  and 
the  kephalin  removed  from  the  ether  solution  by  precipitation  with 


absolute  alcohol,  there  remains  a  bulky  solution  containing  all 
lecithin,  much  sphingomyelin,  and  some  kephalin,  together  with 
the  cholesterin  previously  contained  in  the  white  matter.  When 
to  this  solution  CdCl2  is  added,  a  voluminous  precipitate  ensues, 
which,  after  washing,  yields  to  ether  a  quantity  of  coloured  salt. 
This  after  concentration  is  precipitated  by  alcohol,  and  purified 
by  repetition  of  this  treatment.  The  composition  of  this  precipi- 
tate is  shown  in  the  following  summary  of  analyses  : 

In  100  of 

Per  cents,  found.  -r-  by  At.  Wts.  -^Cd  as  1.  organic  matter. 

C    48-12  ]  4-01  42-21  58'71 

H     7-55   \  7-55  79-47  9-21 

N     1-43   \  81-95    0-102  1-07  1-74 

P     3-524  I  0-113  1-18  4-30 

O    21-33  J  1-33  14-00  26-02 

Cd  10-65   \  0-095  1-00  99-98 

CI     7-40   /  ^    0-208  2-18 

100004  100-00 

leading  to  formula  C^gH^gNPOj^,  CdCl2. 

This  compound  is  noteworthy  on  account  of  two  features,  viz., 
that  it  coincides  with  the  composition  of  the  theoretical  CdCl^ 
salt  of  kephalin,  plus  one  atom  of  oxigen,  and  that  the  CdCl^  is  a 
complete  molecle,  combined  with  an  ap^^arently  complete  molecle 
of  organic  matter.  Such  compounds  as  this  and  the  ones  to  be 
described  hereafter  with  15  atoms  of  oxigen,  make  one  regret 
that  there  are  no  means  of  determining  oxigen  directly  in  organic 
chemistry.  The  oxigen  is  estimated  by  the  void  left  by  the  sub- 
stances determined,  and  this  gives  an  opportunity  for  small  im- 
purities to  be  summed  up  under  the  guise  of  this  element.  Now 
the  substance  here  considered  had  not  undergone  the  process  of 
purification  by  water,  filtration,  and  acid,  and  it  may  therefore 
have  been  kephalin  to  which  some  slight  impurity  was  attached. 
On  the  other  hand,  there  is  no  proof  of  the  existence  of  such  im- 
purity, and  none  could  be  found  by  testing.  It  is  therefore 
necessary  to  consider  this  substance  as  a  genuine  compound  of  a 
kephalin  containing  an  atom  of  0  more  than  the  normal  kephalin, 
to  which  it  will  be  convenient  to  apply  the  term  oxikephalin.  In 
any  case  the  isolation  of  this  body  from  the  mother-liquor  of 
kephalin  by  the  ether  process,  by  means  of  CdClg  is  of  sufficient 



importance  in  itself,  no  matter  how  the  question  of  the  atom  of 
oxigen  may  ultimately  be  decided  by  further  research. 

Behaviour  of  a  similai-  Salt  with  Water. — A  portion  of  a  salt 
similarly  obtained,  though  not  analysed,  was  digested  with  w^Jer, 
whereupon  it  began  to  swell,  and  the  water  after  filtration  was 
found  to  contain  large  quantities  of  CdCU,  proved  expressly  by 
the  hydrothion  and  silver  tests.  When  the  extraction  with  water 
had  been  continued  for  some  time  filtration  was  effected,  when 
during  washing  the  body  swelled  to  such  an  extent  as  to  clog  the 
filter.  There  was  therefore  no  guarantee  of  its  purity  from  CdCl^. 
The  experiment  proves  that  by  simple  digestion  with  water  much 
CdClg  is  extracted,  but  the  entire  amount  can  only  be  removed  by 
a  \oT\g  process  of  dialysis  in  corrugated  filters  of  vegetable  parch- 
ment. The  compound  cannot  be  freed  from  cadmium  by  H^S,  as 
when  so  treated  in  ether  solution  it  only  assumes  a  yellow  colour, 
and  the  CdS  remains  dissolved.  This  peculiar  bearing  is  ob- 
served by  several  phosphorised  compounds. 

d.  Peroxikephalin,  C^^yj^VOy^. 
A  quantity  of  kephalin,  obtained  after  frosting  the  ether  solu- 
tion and  precipitating  it  by  absolute  alcohol,  was  subjected  to 
elementary  analysis,  without  having  undergone  the  water  filtration 
and  HCl  process,  and  gave  results  of  which  the  following  is  a 
summary  : 

In  100.  ^  by  At.  Wts.       -r-  by  N  =  1. 

C    57-750  4-8125  42-85 

H     8-902  8-9020  79-26 

N     1-573  0  1123  1-00 

P     3-680  0  1187  1-05 

0   28-095  1-7560  15  63 

leading  to  formula  C^.^H^gNPOi^ ;  at.  w.  =  868. 

Transformation  of  this  Body  into  Lead  Salt. — About  10  g.  of  the 
analysed  substance  were  dissolved  in  ether,  and  to  this  solution  a 
warm  alcoholic  sohdion  of  lead  acetate  was  added.  A  viscous  pre- 
cipitate was  produced,  which  settled  in  a  mass.  The  lead  acetate 
was  not  used  in  excess,  the  addition  being  discontinued  while 
there  was  still  a  little  matter  in  solution  admitting  of  precipita- 
tion. The  mother-liquor  was  poured  off,  the  mass  of  the  precipi- 
tate was  stirred  and  rinsed  with  a  little  ether  first,  and  afterwards 
with  absolute  alcohol.  The  precipitate  was  now  digested  with  a 
quantity  of  ether,  which  dissolved  much  and  left  a  portion  un- 


dissolved,  which  was  disregarded.  The  solution  was  filtered  off 
and  precipitated  by  absolute  alcohol,  the  precipitate  was  washed 
four  or  five  times  with  absolute  alcohol,  dried  and  analysed. 

The  compound  dried  at  80°  C.  was  fused  with  soda,  nitre,  and 
carbonate  mixture,  the  lead  precipitated  by  H2S,  and  the  PbS 
transformed  into  PbSO^  by  ignition  with  HNO3  and  H^SO^. 

Summary : 

Per  cent,  found  requires 

C    38-337  39-436 

H     5-760  5-868 

N     0-9755  1-095 

P     2-717  2-425 

0    20-312  18-782 

Pb  31-869  32-394 

100-000  100-000 
It  w411  be  seen  by  a  comparison  of  the  oxigen  quantities  in  the 
free  body,  with  those  of  the  salt,  that  there  is  no  reason  for 
assuming  lead  to  be  present  as  oxide  ;  on  the  contrary,  the  H 
being  less  in  the  organic  part  of  the  lead  salt  than  in  the  free  body 
justifies  the  assumption  of  a  substitution  of      by  Pb2. 

Comparison  of  the  Organic  Matter  in  the  Lead  Salt,  with  the  Com- 
position of  the  Free  Body  and  of  the  Organic  Matter  in  a  Salt  of 
Kephaloidin  with  CdCl^. 

Per  cent,  found  in  original  Per  cent,  found  in  CdCl,    Per  cent,  found  in  lead 
free  peroxikephalin.  salt  of  kephaloidin .        salt  of  peroxikephalin. 

C    57-75  57-91  56-31 

H     8-90  8-82  8-30 

N     1-57  1-67  1-43 

P     3-68  3-71  3-98 

O    28-09  27-78  29-81 

The  phosphorus,  as  in  nearly  all  analyses,  is  found  somewhat 
too  high,  rising  in  the  lead  salt  to  5  as  compared  with  N  as  4. 
But  on  the  whole  the  change  by  the  removal  of  some  insoluble  salt 
is  not  so  great  as  to  negative  the  assumption  that  the  free  body 
and  body  contained  in  the  lead  salt  have  essentially  the  same  com- 
position, more  particularly  the  proportion  of  oxigen  has  not  been 
decreased  hij  the  comhination. 

e.  Kephaloidin. 

Definitior\.. — The  substance  thus  designated  is  much  like  kephalin 
as  above  described  and  may  be  identical  in  composition  with  it, 



but  presents  some  slight  differences,  which  necessitate  a  pre- 
liminary distinction.  It  is  obtained  from  buttery  matter  ;  kephalin 
from  white  matter.  It  is  more  fluid  than  kephalin  when  first 
precipitated,  and  never  dries  to  the  same  hard  brittle  substance 
as  kephalin,  but  presents  a  fused  appearance.  It  presents  the 
same  irregularities  in  its  combinations  as  kephalin ;  it  farms 
oxikephaloidin,  which,  like  oxikephalin,  combines  with  a  molecle 
of  CdCl.,,  forming  a  pretty  concise  salt. 

Solubilitj/  in  Water  and  Filtration. — Five  g.  of  dry,  hard,  but 
plastic  kephaloidin  were  dissolved  in  500  cc.  of  cold  water  with 
trituration.  The  substance  became  mucous  at  first,  and  on  agita- 
tion in  a  long  cylinder  was  disintegrated,  and  a  turbid  emulsion- 
like solution  resulted.  This  was  passed  through  the  pressure-filter, 
and  passed  easily  ten  layers  of  English  filtering-paper.  Next  ten 
layers  of  Swedish  paper  were  employed,  when  an  entire  atmosphere 
of  pressure  allowed  the  liquid  to  pass,  but  slowly. 

Bearing  in  Dialysmg  Apparatus. — First  Experiment.— The  fore- 
going solution,  after  filtration  and  subsequent  treatment  with 
animal  charcoal,  which  did  not  make  it  clear,  was  distributed  over 
two  dialysers  of  parchment-paper.  After  twenty-four  hours  the 
dialysate  gave  but  slight  evidence  of  containing  kephaloidin,  by 
giving  a  mere  vestige  of  precipitate  with  lead  salt,  while  the 
original  solution  gave  a  very  copious  precipitate.  Only  a  very 
minute  portion  of  matter,  therefore,  had  passed  the  diaphragm. 

Second  Experiment. — A  solution  and  emulsion  of  about  20  g.  of 
kephaloidin  in  500  cc.  of  water  was,  without  having  been  filtered, 
subjected  to  dialysis.  After  twenty-four  hours  only  a  very  small 
quantity  of  kephaloidin  had  j)assed,  as  shown  by  the  lead  precipi- 
tate. The  original  solution  on  the  dialyser  gave  a  copious  thick 
precipitate  with  the  same  lead  salt.  It  was  thus  shown  that  a 
1  per  cent,  solution  can  hardly  be  dialysed,  while  a  per  cent, 
solution  dialyses  a  little,  but  not  enough  for  practical  purposes. 
Kephalin  and  kephaloidin  act  in  watery  solution  like  colloids,  and 
remain  on  the  dialyser,  while  allowing  the  crystalloids  mixed  or 
combined  with  them  to  pass  in  the  pure  water.  They  act  as 
dialysers  themselves  when  placed  in  pure  water,  and  yield  up 
the  soluble  salts  or  bases  or  acids  with  which  they  are  combined. 
Dialysis  by  vegetable  parchment  is  effective  in  completing  this 

Bearing  of  the  Ellier  Solution  icith  Water. — The  kephaloidin  was 


twice  precipitated  by  alcohol  from  ether  solution,  and  then  redis- 
solved  in  ether.  A  few  drops  falling  in  water  are  precipitated, 
and  on  shaking  a  turbid  emulsion  is  formed.  Boiling  transforms 
this  into  a  turbid  mucous  mass  w^ith  thick  and  viscid  flakes. 
Hydrochloric  acid  added  to  this  emulsion  causes  white  curdling, 
and  the  white  flakes  can  with  difficulty  be  filtered  off.  The 
filtrate  is  white  and  turbid. 

Water,  hydrochloric  acid,  and  ether  in  certain  proportions  pro- 
duce a  thick  white  jelly;  a  little  more  ether  separates  oily  ether 
solution,  which  gives  no  precipitate  with  alcohol,  or  in  this 
mixture  with  CdCl^,  and  contains  therefore  HCl. 

Ether  solution  mixed  with  little  water  becomes  a  solid  white 
mass;  more  water  produces  curds,  ultimately  emulsion  and 

Kephaloidin  is  easily  soluble  in  benzol ;  treated  with  HCl  gas, 
this  solution  changes  colour,  but  gives  no  precipitate ;  alcohol 
added  to  this  gives  a  little  precipitate,  soluble  in  excess ;  ether 
gives  no  precipitate  in  the  benzol  HCl  solution.  A  solution  of 
kephaloidin  in  anhydrous  ether  is  not  precipitated  by  benzol. 

Reactions  of  the  Watery  Solution  of  Kephaloidin  : 

Hydrochloric  acid  produces  a  dense  slightly  yellow  precipitate, 
Avhich  after  isolation  is  soluble  in  ether  and  not  precipitated 
by  alcohol.  In  the  ethereal  solution  of  HCl  precipitate, 
alcoholic  PtCl^  produces  a  precipitate  soluble  in  ether  and 
reprecipitated  by  alcohol. 

Sulphuric  acid  produces  a  precipitate  like  that  by  HCl. 

Nitric  acid,  same  as  sulphuric. 

Barita  water  ^ 

Lime  water  (  All  produce  good  precipitates  which  coalesce 

Cadmium  chloride  i'      well  on  standing  or  agitation. 
Zinc  chloride  j 

Mercuric  nitrate  gives  a  good  curdled  precipitate  insoluble  in 

HNO3,  but  made  slightly  yellow  thereby. 
Barium  chloride  also  produces  a  good  flaky  precipitate.  This 

body  after  isolation  is  insoluble  in  water  and  absolute  alcohol, 

but  readily  soluble  in  ether. 
Platinum  chloride  gives  a  complete  precipitate. 
Lead  acetate  gives  a  good  precipitate. 
Mercuric  acetate  gives  a  very  voluminous  precipitate. 
Cupric  acetate,  a  whitish  flocculent  precipitate. 

Kephaloidin  Lead. — A  specimen  of  kephaloidin  which  had  been 
frozen  in  the  ethereal  solution,  and  precipitated  by  alcohol,  was 


once  more  dissolved  in  ether,  and  placed  in  a  freezing  mixture 
for  twenty-four  hours.  No  deposit  occurred.  This  ether  solution 
also  gave  the  reactions  above  described,  and  with  silver  nitrate  its 
watery  solution  gave  a  copious  white  precipitate.  The  ether 
solution  was  poured  slowly  in  a  thin  stream  into  absolute  alcohol, 
when  the  kephaloidin  was  precipitated  as  a  viscid  mass.  The 
whole  of  this  was  dissolved  in  water,  and  lead  acetate  added ;  a 
copious  precipitate  ensued,  which  was  filtered  and  washed,  ex- 
tracted with  warm  dilute  alcohol,  ultimately  with  warm  absolute 
alcohol ;  it  then  dissolved  in  ether  without  residue,  was  precipitated 
by  absolute  alcohol,  became  pulverulent,  was  dried  in  vacuo,  and 

Summary.  matS""     Theory  of  C,,H,,NPO,, 

C    50-983  1  60-88  60-28 

H     7-721  I  rp  ,  1  9-22  9-44 

1  A1-  I  iotal  organic  .  r,- 

N     1-01,  >.      go  -  «  1-21  1-6/ 

P     3-666  I       ^'^  4-37  3-70 

O    20-353  J  24-32  24-885 

Pb  16-260  16-260     

    100-00  100-000 

100-000  100-000 

It  is  at  once  evident  that  the  Pb  stands  in  no  simple  proportion 
to  any  other  element.  Kephalin  lead  if  dibasic  would  require 
19  per  cent.,  if  monobasic  11  per  cent.,  of  Pb.  The  molecle  of 
the  kephaloidinate  contains  thus  rather  more  than  half  a  molecle 
of  Pb,  and  is  consequently  a  mixture  of  lead  salt  with  free  body. 
There  is  also  an  irrationality  perceptible  on  the  P,  which  is  too 
high,  and  the  N,  which  is  too  low.  But  on  the  whole  the  consti- 
tution, properties,  and  products  coincide  with  those  show^n  by 
kephalin  of  the  compared  formula. 

/.  Oxikej^haloidin  ivifh  Cadmic  Chloride,  2(C^.H-.NPOi4) +  CdCl,. 

In  this  case  a  quantity  of  kephaloidin  obtained  by  the  ether 
process,  not  purified  by  water,  filtration,  and  HCl,  etc.,  was  trans- 
formed into  CdCl,  salt,  and  precipitated  by  alcohol ;  redissolved 
in  ether,  and  the  solution  repeatedly  frozen,  and  freed  from  some 
deposit,  then  precipitated  by  absolute  alcohol.  It  could  be  dried 
at  80°  C.  without  change. 


Summary  of  analyses  per  cent,  : 

C       52-796  V 




?  Ia^  I  Total  organic 

3-690.  ^^^^^ 





leading  to  formula  C^gH^^NPOi^  for  organic  matter.  If  one  atom 
of  CdCl2  were  combined  with  two  atoms  of  organic  body,  then 
9 -8  per  cent.  CdCl2  should  have  been  present. 

Comparison  of  the  Composition  of  the  Organic  Matter  with 
Per  cents,  of 

Organic  matter  of 
oxikephalin  with 

C  58-71 

H  9-21 

N  1-74 

P  4-30 

0  26-02 

Organic  matter  in 
with  CdCIa- 

.  27-45 

Free  per- 



Organic  matter  in 
lead  salt  of 





It  will  thus  be  perceived  that  the  oxikephaloidin  is  inter- 
mediate between  oxikephalin  and  peroxikephalin  in  composition 
in  all  items  except  alone  hydrogen.  This  peculiar  anomaly,  if 
such  it  be,  must  be  reserved  for  future  deliberation.  The 
empirical  formula  expressing  the  composition  of  this  salt  is 
2(C,,H„NP0i,)  +  CdCl,. 

The  ethereal  solution  of  this  salt  was  not  precipitated  by 
hydrothion  gas  passed  through  it. 

. '  g.  Decompositions  of  Kephalin. 

When  pure  kephalin  in  the  perfectly  dry  state  is  heated  in  a 
water-oven  to  between  90°  and  100°  it  fuses  to  a  dark  red 
transparent  viscid  oil.  It  becomes  solid  again  on  cooling,  but 
retains  a  viscosity,  so  as  to  adhere  to  the  fingers,  which  it  did  not 
before  it  was  heated.  Treated  with  water,  the  heated  and  cooled 
kephalin  swells  again  and  gradually  dissolves,  but  is  darker 


coloured,  so  that  some  slight  degree  of  decomposition  or  of  oxida- 
tion seems  to  have  taken  place. 

When  heated  to  higher  temperatures  it  gives  out  much  heavy 
strongly  smelling  inflammable  vapour,  which  partially  burns,  with 
formation  of  much  soot.  Ultimately  a  bulky  charcoal  is  left, 
which  cannot  by  ordinary  heating  in  platinum  vessels  be  entirely 
destroyed,  as  it  is  soaked  with  phosphoric  acid.  It  cannot  be 
entirely  burned,  even  after  the  principal  quantity  of  phosphoric 
acid  has  been  extracted  with  water.  Complete  combustion  is 
effected  only  in  the  presence  of  nitre. 

With  concentrated  sulphuric  acid  dry  kephalin  in  fine  particles 
immediately  assumes  a  dark  red-brown  colour,  which  gradually 
becomes  nearly  black.  When  sugar  and  sulphuric  acid  are  allowed 
to  act  upon  kephalin,  a  reaction  similar  to  the  one  given  by  bile- 
acids  is  gradually  engendered.  But  the  process  essentially  requires 
time,  during  which  the  mixture  passes  through  a  stage  of  dark- 
brown  colour,  until  a  deep  purple  is  at  last  attained.  But  this 
colour  is  never  so  pure  or  beautiful  as  that  obtained  with  cere- 
brosides,  myelin,  or  the  bile-acids.  It  is  therefore  probable  that  a 
decomposition  of  the  kephalin  has  to  be  effected  before  the  reaction 
is  attained. 

A.  Chemohjses  of  KejyhaUns. 

a.  Limited  Chemolysis  hij  Caustic  Soda. — A  watery  solution  con- 
taining 30  g.  of  pure  kephalin,  filtered,  etc.,  was  precipitated  by 
HCl.  The  pulpy  deposit  was  put  into  a  flask,  and  a  solution  of 
5  g.  crystallised  soda  hydrate  added.  The  precipitate  disappeared 
on  agitation,  forming  first  a  gelatinous,  later  a  fluid  solution.  The 
.solution  was  now  placed  in  a  bath,  and  heated  gentl}^  for  nine 
hours.  During  the  process  it  was  observed  that  skins  formed  on 
the  surface  similar  to  membranes  on  milk  while  being  heated.  On 
cooling,  the  liquid  formed  a  gelatinous  cake,  consisting  of  viscous 
curds  set  in  a  thinner  fluid.  Next  day  the  mixture  was  boiled 
during  nine  hours  on  a  sand-bath.  Bumping  was  mitigated  by 
dropping  a  spiral  of  platinum  into  the  fluid.  Great  frothing 
ensued,  which  was  opi)osed  by  a  funnel  fixed  upon  the  top  of  the 
flask  by  a  cork,  and  supported  by  a  stand.  After  this  boiling  the 
liquid  was  still  tur])id,  became  gelatinous,  viscid,  and  set  on 
cooling,  and  covered  by  a  membrane.    On  commotion  it  showed 


the  wavy  glistening  appearance  of  soaps,  and  when  at  repose  in  a 
beaker  formed  folds  as  from  a  tubular  membrane  sinking. 

Reactions  of  the  Soapy  Solution. — It  was  insoluble  in  water,  and 
not  further  precipitated  thereby.  It  was  curdled  by  cold  alcohol, 
dissolved  by  hot,  leaving,  however,  some  particles  undissolved, 
which  proved  soluble  in  ether.  It  was  not  precipitated  by  concen- 
trated sodium  chloride  solution — i.e.,  not  salted  out. 

Decomposition  of  the  Soaps  hy  Hydrochloric  Acid. — The  soap  was 
now  treated  with  hydrochloric  acid,  until  a  strongly  acid  reaction 
was  attained,  when  a  whitish-yellow  precipitate  fell,  and  the  fluid 
lost  its  viscosity.  The  precipitate  was  washed  with  water,  and  the 
filtrate  was  evaporated  on  water-bath. 

The  Precipitate  of  Fatty  Acids  on  the  Filter  was  washed,  and  be- 
came very  adhesive,  yet  fatty ;  boiled  in  water  it  did  not  fuse, 
but  agglutinised  a  little  ;  nothing  like  oil  or  fused  fatty  acid 
appeared.  Warmed  on  paper  it  did  not  fuse  like  fat,  and  gave 
only  a  very  slight  grease-stain ;  most  of  it  remained  slightly 
glistening  on  the  surface,  even  when  heated  until  brown.  The 
matter  had  a  fine,  smooth,  greasy  touch  between  the  fingers,  and 
seemed  like  a  fatty  acid  in  a  hydrated,  swelled  state.  It  dissolved 
easily  in  cold  absolute  alcohol,  leaving  a  quantity  of  adhesive  dark 
matter  undissolved.  The  latter  will  not  be  considered  any  further 
in  this  place. 

The  Acids  soluble  in  Alcohol — Kephalophosphoric,  Kephalic,  and  a 
Third  Acid. — The  solution  showed  a  feeble  green  fluorescence;  it 
was  filtered  from  a  slight  secondary  deposit  of  insoluble  acid. 
Alcoholic  acetate  of  lead  w^as  now  added,  w^hich  produced  a  bulky 
nearly  white  precipitate.  This  was  washed  with  absolute  alcohol, 
drained  on  paper,  dried,  and  treated  with  ether.  It  was  entirely 
insoluble  in  ether,  and  constitutes 

Kephalophosphate  of  Lead,  so  named  from  being  the  lead  salt  of 
a  phosphorised  acid  obtained  from  kephalin,  more  complicated 
than  glycerophosphoric  acid.  The  total  quantity  of  salt  obtained 
weighed  6-2  g.  Powdered  and  dried  at  95^  C,  it  baked  together 
a  little  on  surface,  but  when  stirred  remained  pulverulent. 

A  combustion  for  nitrogen  gave  only  a  trace  of  permanent  gas, 
so  that  the  substance  is  proved  to  be  free  from  nitrogen. 

Phosphorus  calculated  from  the  Pb  pyrophosphate  found 
-3-572  per  cent.  P. 


Found  in  100.  -h  by  At.  Wgts.  ^  by  P  =  1 

C    48-2fi2                 4-022  35-3 

H     7-990                7-990  70-1 

Pb  23-840                0  1 151  1-01 

P     3-572                 0  1139  1-00 

0    16-336                 1-021  8-96 


leading  to  formula  Cy^HwQPbPOc,. 

Deducting  the  lead,  and  calculating  the  76-16  per  cent,  of  organic 
matter  as  100,  we  get — • 

-^  by  At.  Wgts.  H-by  P  as  1.  At.  Wgts. 

C    63-369              5-2807  34-9  420 

H    10-491            10-4910  69-3  +  2  72 

P     4-691              0-1512  1-0  31 

O    21-449             1-3405  8-8  144 

100-000  667 

The  atomic  weight  derived  from  the  Pb  pyrophosphate  is  663, 
which  closely  approximates  the  quantity  found  directly. 

The  conclusion  drawn  from  this  experience  was  that  chemolysis, 
with  an  amount  of  alkali  insufficient  to  satisfy  at  least  three 
molecles  of  acid,  developed  from  one  molecle  of  kephalin,  must 
stop  short  of  complete  decomposition,  and  produce  intermediate 
products,  of  which  the  principal  one  is  kephalophosphoric  acid. 
It  is  probably  an  acid  containing  three  acid  radicles  and  an  alcohol 
radicle — 

Kephalyl  ) 

Stearyl       -  Phosphoryl  =  Kephalophosphoric  Acid 
Glyceryl  ) 

but  no  nitrogenised  nucleus,  and  by  further  chemolysis  may  split 
up  into  the  acids  obtained  by  its  side. 

Kephalk  Acid  and  Third  Fatty  Acid,  and  their  Barium  Salts. — 
The  alcoholic  solution,  from  which  kephalophosphate  had  been 
precipitated  by  lead  acetate,  was  distilled  to  about  300  cc.  This 
liquor,  on  cooling  and  standing,  deposited  an  oil,  which  was 
isolated,  and  found  to  float  on  water ;  but  on  boiling,  it  became 
viscous  and  solid  in  the  hot.  Oil  and  liquid  were  treated  with 
ammonia  to  strong  alkalinity,  whereby  a  white  emulsive  solution 
was  produced.  To  this,  water  and  watery  acetate  of  lead  were 
added,  until,  and  as  long  as,  a  precipitate  was' produced.  This 
was  white,  adhesive  and  bulky.    It  was  filtered,  washed,  and 



dried,  powdered,  dissolved  in  ether,  filtered,  decomposed  with 
hj^drochloric  acid  and  water ;  the  ether  solution  was  washed, 
filtered,  and  when  clear  distilled  to  small  bulk.  The  red  solution 
was  treated  with  w-atery  ammonia,  filtered,  barium  chloride  added, 
when  a  bulky  precipitate  was  obtained.  This  was  washed  for  a 
long  time,  until  washings  were  nearly  free  from,  barita  ;  the  pre- 
cipitate was  dried  in  air,  and  treated  with  ether ;  a  coloured  salt 
dissolved  and  a  white  salt  remained  undissolved. 

Coloured  salt,  soluble  in  ether  =  Kephalate  of  barium. 

The  kephalate  of  barium  dissolves  rapidly  and  abundantly  in 
ether,  and  is  precipitated  from  this  solution  by  absolute  alcohol. 
It  is  always  of  a  dark  colour,  which  intensifies  in  the  ether,  pro- 
bably by  oxidation.  The  salt  is  insoluble,  or  but  little  soluble, 
in  boiling  alcohol,  and  is  not  deposited  from  this  solution  as  oleate 
of  barium  is.  The  acid  cannot  be  decolorised  by  animal  charcoal, 
either  when  in  the  state  of  sodium  salt,  or  when  in  the  free  state 
dissolved  in  boiling  alcohol,  and  all  operations  seem  only  to  assist 
in  farthering  its  oxidation.  It  seems  that  its  radicle,  while  in 
the  kephalin,  is  the  principal  cause  of  the  assumption  of  colour 
and  fluorescence  by  that  principle. 

White  salt,  insoluble  in  ether. 

This  barium  salt  appears  very  much  swelled  in  ether  ;  when 
dry  it  is  white  and  pulverulent.  Hydrochloric  acid  and  water 
extract  the  barium,  and  washing  with  water  leaves  the  acid 
soluble  in  ether ;  the  ether  distilled  off  leaves  the  acid  as  a  coloured 
soft  mass,  which  fuses  at  26^,  congeals  at  25°,  and  crystallises  in 
rosettes  like  margaric  acid.  It  dissolves  easily  in  absolute  alcohol, 
forming  colourless  fluid ;  a  few  drops  of  water  added  to  alcohol 
cause  acid  to  separate  as  an  oil  on  top  of  spirit;  on  standing, 
colourless  rosettes  of  crystals  form  in  this  oil,  and  may  be 
separated.    The  spirit  deposits  white  clouds  of  the  acid. 

This  acid  differs  from  oleic  by  its  barium  salt  being  entirely  in- 
soluble in  boiling  alcohol.  It  differs  from  stearic  by  its  lead  salt 
being  soluble  in  ether.  It  is  not  fluid  at  ordinary  temperatures, 
])ut  semi-solid,  and  fuses  only  at  26°,  and  from  concentrated 
spirit  it  is  entirely  separated  and  crystallises,  while  oleic  acid 
remains  dissolved  in  such  spirit,  and  does  not  crystallise  at  such 

In  the  manipulation  of  these  acids  in  the  presence  of  absolute 


alcohol  the  formation  of  ethylic  ethers,  which  easily  ensues,  has 
to  be  carefully  avoided. 

Glycerophosphoric  Ac/d. — The  acid  filtrate  containing  that  phos- 
phorus which  was  not  combined  with  the  kephalophosphoric  acid  in 
the  form  of  glycerophosphoric  acid,  some  nitrogen  in  an  unknown 
form,  the  sodium  chloride,  together  with  some  free  hydrochloric 
acid,  Avas  evaporated  to  a  low  bulk,  and  its  acidity  carefully 
neutralised  by  caustic  soda.  Acetate  of  lead  was  now  added  as 
long  as  a  precipitate  was  produced,  and  the  white  deposit  was 
filtered  off.  It  was  boiled,  filtered,  and  washed  with  hot  water, 
decomposed  with  H^S,  the  filtrate  neutralised  with  calcium 
carbonate  and  lime  water,  filtered  and  evaporated.  When  con- 
centrated the  solution  deposited  crystalline  calcium  ghjcero- 

Nearin  and  Second  Oily  Base. — The  solution  from  which  glycero- 
phosphoric acid  has  thus  been  removed  was  freed  from  lead 
by  H^S,  the  acetate  was  decomposed  by  repeated  addition  of 
hydrochloric  acid  and  evaporation  to  dryness,  and  the  crystalline 
magma  was  treated  with  absolute  alcohol  to  extract  the  hydro- 
chlorate  of  the  expected  nitrogenised  body.  To  this  alcoholic 
solution  PtCl^  was  added,  when  a  slight  yellow  precipitate  ensued, 
which  was  separated  by  filtration,  washed  with  alcohol,  and  dried. 
It  was  neurin-hydrochlorate-platinic  chloride.  It  could  only  repre- 
sent a  small  portion  of  the  nitrogen  contained  in  the  chemolysed 
kephalin ;  as  the  volatilised  vapours  had  not  been  collected,  some 
volatile  alkali  may  have  escaped  unnoticed.  The  alcoholic  mother- 
liquor  of  this  platinum  precipitate  was  freed  from  platinum  by 
H.,S.  Evaporated,  it  left  a  syrupy  residue  ;  this  was  again  treated 
with  little  alcohol  and  PtCl^,  and  a  slight  deposit  removed.  The 
liquor  on  addition  of  much  ether  deposited  an  oily  hody,  soluble  in 
absolute  alcohol,  reprecipitated  by  ether.  Distilled  with  dilute 
H.,SO_^  and  MnO^,  it  gave  a  distillate  which  smelled  of  acetic  acid, 
and  after  neutralisation  by  soda,  was  reduced  by  AgNO^  and  by 
HgNO..,  consequently  contained  formic  acid.  These  may  be  con- 
sidered as  decomposition  products  of  glycerol,  or  of  a  body  contain- 
ing its  radicle. 

Summary  of  llesidts  of  First  Chemolysis  of  Kephcdin. — All  first 
products  are  soluble,  the  soaps  imperfectly  in  water.  Hydrochloric 
acid  precipitates  a  mixture  of  fatty  acids. 

1.  Kephalophosphoric  acid,  consisting  probably  of  kephalic,  a 


second  fatty  acid,  and  glycerol  and  phosphoric  acid,  yet  in  com- 
bination, therefore  imperfectly  chemolysed. 

2.  Kephalic  acid. 

3.  A  second  fatty  acid. 

4.  Glycerophosphoric  acid. 

5.  Ammonia. 

6.  Glycerin. 

7.  A  base  giving  oily  PtCl^  salt,  and  being  perhaps  glyceramin 
of  a  new  type.  Its  solubility  in  water,  alcohol,  as  hydrochlorate 
and  as  PtCl^  salt  is  very  great,  and  its  precipitation  by  ether  by 
no  means  complete. 

(3.  Complete  Chemolysis  of  Kephalin  by  Caustic  Soda. — 40  "7  g.  of 
kephalin,  purified  by  the  water  solution,  filtration,  and  HCl 
process,  as  before  described,  were  mixed  with  5  g.  of  crystalline 
soda  hydrate  dissolved  in  two  litres  of  water.  The  same  pheno- 
menon was  observed  during  the  boiling  as  in  the  first  experiment. 
The  boiling  was  continued  during  about  eighteen  hours,  of  which 
three  hours  took  place  in  water -bath,  and  the  other  fifteen  hours 
on  sand-bath,  the  time  taken .  to  heat  it  to  boiling  on  the  three 
days  during  which  experiment  lasted  not  included.  While  on 
the  first  and  second  day  the  mixture  had  set  into  a  jelly,  it  did 
after  the  last  boiling  not  become  gelatinous  again,  but  remained 
a  somewhat  turbid  thick  fluid.  To  this  HCl  was  added  until  the 
precipitate  was  curd}?  and  the  fluid  strongly  acid.  The  precipi- 
tate was  separated  by  the  filter.  It  could  be  washed  but  im- 
perfectly, as  after  consolidation  on  the  filter,  the  precipitate  set 
into  a  gelatinous  tremulous  solid  mass  which  allowed  no  washing 
water  to  pass.  This  mass  of  acids  was  placed  into  a  wide- 
mouthed  bottle,  shaken  with  water,  and  treated  with  caustic 
ammonia.  It  formed  a  complete  solution,  "which  was  filtered  on 
hot  funnel  and  left  no  trace  of  residue.  The  solution  was  opaque, 
and  on  agitation  showed  the  silky  clouds  common  to  soaps.  To 
this  solution  acetate  of  lead  was  added  until  the  precipitate  was 
curdy,  and  the  liquid  distinct  and  filterable.  It  was  now  passed 
through  French  filtering-paper,  and  the  precipitate  washed*  with 
much  water,  being  agitated  constantly  with  a  glass  rod,  so  that  all 
parts  were  well  penetrated  by  water.  When  the  filtrate  was  free 
from  chlorine  and  from  lead  (from  excess  of  acetate), the  precipi- 
tate was  allowed  to  drain  on  paper  and  a  cloth  and  dried.  It 
took  many  days  to  dry,  being  frequently  crushed  and  stirred. 


Ether' extracted  a  coloured  body,  and  left  a  white  salt  insoluble. 
This  was  separated  by  filtration,  and  washed  by  being  twice 
removed  from  filter,  and  shaken  in  a  bottle  with  ether.  Filtration 
was  always  difiicult,  owing  to  the  finely  divided  state  of  the  salt. 

The  white  Ph  Salt  insoluble  in  Ether  was  dried  in  the  vacuum,  and 
after  preliminary  analysis  was  further  transformed  into  barium 
salt  by  HCl,  water,  and  ether,  solution  of  acid  in  NH^HO,  and 
precipitation  by  BaCl^.  The  salt  was  extracted  by  boiling 
alcohol,  and  what  remained  insoluble  was  analysed.  It  was  found 
to  be  principally  stearate. 

The  coloured  Ph  Salt  soluble  in  Ether  was  red  in  transmitted  light, 
and  fluoresced  green,  altogether  appeared  like  a  solution  .  of 
kephalin.  It  was  concentrated  by  distillation,  and  the  solution 
precipitated  by  absolute  alcohol ;  a  viscous  salt  fell  down,  which 
became  hard  in  alcohol,  was  drained  and  dried  in  vacuo.  After 
preliminary  testing,  it  was  transformed  into  Ba  salt  by  HCl,  water 
and  ether  ;  solution  of  acid  in  NH^HO  and  precipitation  with 
BaCl2 ;  solution  in  ether  and  precipitation  by  alcoriol.  It  was 

Treatment  of  the  Filtrate  containing  Glycerophosphork  Acid  and 
Ammonium  Base. — It  was  neutralised  with  barita  water,  of  which 
a  slight  excess  was  added.  A  saturated  solution  of  lead  chloride 
in  water  was  now  added,  which  produced  a  flocculent  white  pre- 
cipitate of  glycerophosphate.  The  advantages  of  the  lead 
chloride  were  that  no  new  acid  was  introduced  into  the  fluid,  from 
which  the  ammonium  base  had  yet  to  be  extracted.  The  fluid 
became  slightly  acid,  and  was  corrected  by  barita  water  cautiously 
added.  When  all  was  precipitated  the  glycerophosphate  of  lead  was 
filtered  off",  washed,  and  dried.  The  mother-liquor  was  concen- 
trated, and  then  gave  another  not  inconsiderable  precipitate  with 
lead  chloride  solution.  The  reaction  was  continued  until  a 
filtered  sample  of  liquid  remained  clear  with  the  chloride,  and  the 
second  precipitate  was  isolated  and  united  with  the  primary  one. 
The  previously  feebly  alkaline  liquid  was  now  feebly  acid  ;  it  was 
evaporated  to  a  low  bulk  and  then  to  dryness.  It  was  now  dis- 
solved in  a  minimum  of  water,  and  precipitated  with  absolute 
alcohol,  until  this  reagent  produced  no  further  turbidity,  and  no 
deposit  on  standing  twelve  hours.  The  alcoholic  extracts  were 
united,  concentrated,  and  precipitated  with  PtCl^.  A  yellow  pre- 
cii)itate  fell,  which  will  be  described  further  on. 


^  The:.GlyceropJiosphafe  of  Z^^c? "dried  to  a  hard  slightly  coloured 
mass.  (This  hardening  of  glycerophosphates  is  also  observed  upon 
barium  ^altj  and  >he  condition  must  be  borne  in  mind  when  it  is 
subsequently  intended  to  decompose  these  salts.)  It  was  re- 
peatedly crushed,  ultimately  powdered,  and  dried  in  water-oveh. 
The  total  weighed  7*4435  g.  Now  assuming  the  40-7  g.  kephalin 
to  have  contained  (at  4*2  per  cent.  P)  1*7  g.  phosphorus,  then  this 
corresponds  to  19 '38  g.  glycerophosphate  of  lead,  of  which  theory 

Acid.  Pb  salt.  Pb  pyrophosphate. 

3C    36  36  — 

9H     9  7  — 

P    31  31  2P  62 

6  0    96  96  7  0  112 

172  Pb  207  2  Pb414 

377  588 

But  as  only  7*4435  g.  were  obtained  there  is  a  deficiency  of 
11*9365  g.  Thus  much  was  therefore  decomposed  further  into 
phosphoric  acid  and  glycerol. 

In  order  to  ascertain  approximately  the  purity  of  the  lead 
glycerophosphate,  0*9110  g.  was  burned  until  white,  and  left 
0*7440  g.  Fh.,V.p^,  while  theory  required  0*7104.  The  white 
residue  was  treated  with  acetic  acid  and  found  insoluble  in  it, 
which  corresponds  with  pyrophosphate. 

The  lead  salt  was  now  decomposed  with  hydrothion,  the  filtrate 
treated  with  CO2  in  the  cold  to  expel  H2S,  and  then  with  milk  of 
lime  to  alkalinity,  filtered  and  treated  with  some  CO^.  The 
filtrate  after  twelve  hours'  standing  was  evaporated  near  the 
boiling-point,  and  filtered  hot  from  the  white  precipitate  of  calcium 
glycerophosphate.  This  when  dry  weighed  only  0*727  g.  Of  this 
0*3400,  after  strong  ignition  with  HNO3,  left  0*207  g.  residue, 
equal  to  60*8  per  cent.  Csi.^P.fl^.  Pure  glycerophosphate  should 
leave  60*5  per  cent,  of  pyrophosphate. 

Acid  Glycerophosphate  of  Calcium. — The  aqueous  filtrate  from 
which  the  above  salt  had  been  removed  whilst  hot,  was  mixed 
with  three  volumes  of  alcohol,  when  a  light  bulky  precipitate 
ensued.  This  was  isolated  by  filtration,  washed  with  alcohol  and 
dried.  It  weighed  0  526  g.  Of  this  0  2446  g.  gave  0*1250  g.  pyro- 
phosphate, equal  to  51*1  per  cent,  residue.  This  corresponds  to  a 



salt  which  might  be  obtained  from  acid  glycerophosphate  of  calcium 
by  combustion. 

CgH.CaPO,  +  CaH^POg  =  CgHieCaPPi^  =  acid  glycerophos- 
phate of  calcium. 

This  on  combustion  may  lose  C^Hj^Og,  and  leave  H.j^diVjd^,  or 
half-saturated  acid  pyrophosphate  of  calcium,  or  a  body  isomeric 
with  it.  By  this  theory  56*54  per  cent,  residue  should  be  left, 
which  differs  so  much  from  51 '1  per  cent,  found,  that  we  must 
suppose  the  salt  to  have  been  one  of  those  peculiar  alcoholo- 
hydrates  which  salts  of  glycerophosphoric  acid  are  prone  to  form, 
as  will  be  specially  proved  lower  down.  There  also  the  actual 
production  of  the  acid  calcic  glycerophosphate,  here  for  the  first 
time  theoretically  assumed,  will  be  proved  by  further  experiments 
and  analyses. 

The  quantity  of  glycerophosphoric  acid  lost  in  the  process  of 
transformation  is  enormous,  and  this  is  invariably  observed  in  all 
experiments  which  I  have  made. 

The  Flatinic  Chloride  Precipitate. — The  yellow  precijiitate  was 
washed  with  absolute  alcohol.  On  drying  it  became  horny, 
crumbled  up,  was  viscous  outside  and  discoloured,  and  ad- 
hered strongly  to  the  paper.  Water  restored  yellow  colour 
and  pulverulence.  It  dissolved  in  hot  water,  of  which  much 
was  required.  On  cooling,  brilliant  small  crystals  were  de- 
posited amounting  to  0*9428  g.  This  by  analysis  proved  to  be 
almost  pure  ammonium  salt,  containing  only  a  trace  of  potassium, 
which  raised  the  residue  left  on  combustion  to  45*56  per  cent., 
while  44*36  per  cent,  are  required  by  pure  NH^  salt.  By  evapor- 
ation over  H^SO^  two  further  small  crops  of  ammonium  salt  were 
obtained  ;  the  rest  of  the  solution  dried  up  to  a  thick  liquid  and 
did  not  crystallise. 

The  filtrate  from  the  PtClj^  scdt  was  mixed  with  a  large  excess  of 
ether  until  this  produced  no  further  turbidity.  An  oihj  matter 
settled,  which  was  purified  by  repeated  solution  in  alcohol  and 
precipitation  by  ether.  It  was  not  analysed,  as  there  were  no 
guarantees  of  its  purity.  It  was  distilled  with  H^SO^  and 
MnO.„  and  yielded  an  acid  distillate,  in  which,  after  neutralisation 
with  soda,  the  presence  of  formic  acid  was  signalised  by  the  usual 

This  platinum  salt,  which  from  the  reactions  detailed  may  split 
up  into  glycerol  and  ammonia,  reduces  the  platinum  rapidly  when 


left  in  contact  with  ether- alcohol,  and  becomes  black.  Altogether 
this  product  is  one  of  the  most  difficult  matters  to  treat,  and  par- 
ticularly as  it  is  only  obtained  in  small  quantities. 

7.  First  Chemolijsis  of  Kejjhaliti  with  Barita  Hydrate. — -The 
kephalin  was  prepared  by  the  HCl  process,  and  well  washed  with 
water.  The  quantity  used  was  27 "8  gr.  It  was  placed  in  a  flask 
connected  with  a  condenser,  and  a  solution  containing  80  gr. 
barium  hydrate  was  added.  The  mixture  was  boiled  during 
five  hours  on  a  sand-bath,  when  the  precipitate  became  adhesive 
and  flask  cracked.  After  cooling  and  filtering  the  residue  was 
twice  boiled  with  water,  during  which  it  became  quite  soft  and 
semifluid  ;  it  was  again  thrown  on  a  filter  and  washed  to  neutrality. 
The  washings  were  united  with  the  first  filtrate. 

The  barium  salts  being  drained  of  water,  were  rubbed  in  a  mortar 
with  ether,  and  then  shaken  in  a  bottle  with  much  ether.  The 
ether  dissolved  a  coloured  salt,  leaving  a  tchite  salt  undissolved,  from 
which  the  solution  was  separated  by  filtration. 

The  insoluble  ivhite  salt  was  dried  in  air  ;  later  in  -s'acuo.  It  was 

The  soluble  coloured  salt  had  the  appearance  of  kephalate,  was 
red,  and  fluoresced  green.  The  solution  was  concentrated  and 
precipitated  by  absolute  alcohol.  The  precipitate  was  dried  in 
vacuo,  and  on  subsequent  analysis  was  found  to  be  kephalate. 

The  liquid  containing  the  glycerophosphate  and  ammonium  base  was 
treated  with  carbonic  acid  until  no  more  precipitate  was  produced, 
filtered,  and  the  filtrate  concentrated  on  a  water-bath  nearly  to 
dryness.  During  this  evaporation  it  did  not  deposit  any  salt,  as 
does  the  lime  salt.  The  viscous  mass  was  diluted  with  a  little 
water  to  fluidity,  placed  in  a  bottle,  and  mixed  with  absolute 
alcohol  until  no  further  precipitate  was  produced.  The  precipi- 
tate was  filtered  off"  and  washed  with  alcohol. 

The  precipitate  consisted  of  barium  glycerophosphate.  It  was 
bulky,  white,  and  granular,  probably  alcoholate-hydrate.  On 
standing,  it  contracted,  and  became  horny,  transparent,  and  partly 
fused.  Placed  in  a  glass  dish,  it  fused  entirely  in  a  few  days, 
and  then  dried  to  a  brittle  mass. 



Sammamj  of  Analyses  : 










Formula.  — C3H.BaP0^,H,0. 

The  alcoholic  solution  from  which  the  glycerophosphate  had 
been  removed  was  tested,but  the  products,  being  small  in  quantity, 
"vyere  not  analysed.  Analyses  of  this  part  of  the  products  of  the 
chemolysis  of  kej^halin  are  given  in  the  following  experiment. 

d.  Second  Chemolysis  of  Kejjhalin  by  Barita. — In  this  experiment,  for 
which  a  compound  of  kei^halin  with  cadmic  chloride  was  taken, 
two  sets  of  barium  salts  were  again  obtained,  one  soluble,  the  other 
insoluble  in  ether.  The  salt  which  was  soluble  in  ether  furnished 
a  lead  salt,  which  was  likewise  soluble  in  ether  (28*056  per  cent. 
Pb),  and  insoluble  in,  and  precipitated  by,  ether-alcohol.  The 
salt  which  was  insoluble  in  ether,  when  transformed  into  lead 
salt,  was  found  to  consist  of  two  compounds,  one  insoluble  in 
ether  and  in  alcohol,  the  other  soluble  in  ethei^  but  precipitated 
from  it  b}^  the  addition  of  alcohol. 

The  baritic  solution  was  freed  from  excess  of  barita  hy  car- 
bonic acid,  and  the  filtrate,  after  evaporation  to  a  low  bulk,  was 
treated  with  absolute  alcohol.  A  precipitate  of  barium  glycero- 
phosj^hate  was  obtained,  and  identified  by  quantitative  analysis. 
The  alcoholic  mother-liquor  was  neutralised  with  hydrochloric 
acid,  and  precipitated  with  jjlatinic  chloride.  The  platinum  salt 
so  obtained  was  recrystallised  from  water,  and  ultimately  obtained 
in  brilliant  plates  and  needles. 

Comjmtation  of  Analyses  : 

Percentage.         -^At  Wgts. 


'  C  19-8U1  1-650 

H  4-726  4-726 

N  4-404  -314 

O  4-701  -293 

Pt  32-219  -163 

CI  34-149  -961 


=  (C,Hi,NO),(HCl),PtCl,. 

Neurin  hydrochlorate  i)latinic  chloride. 


Besides  this  salt,  there  was  obtained  from  the  alcoholic  mother- 
liquor  from  which  it  had  been  originally  precipitated,  a  smaller 
quantity  of  a  second  crystallisable  platinic  salt.  After  recrystal- 
lisation  from  water  it  gave  the  following  numbers  on  analysis  : — 

Computation  of  Analyses  : 

Percentages.  -f-At  Wgts.  H-Pt  =  l. 

C       9-158  -763  4-1 

H       3-134  3-134  16-8 

N      5-418  -387  2-0 

0.     6-275  -392  2-1 

Pt    36-718  -186  1-0 

CI     39-297  1-107  5-9 
-  (C2H.NO),(HCl)2PtCl4. 

This  salt  might  be  considered  as  dimethylamin,  in  which  the 
third  atom  of  hydrogen  is  replaced  by  hydroxyl,  or  as  oxethylamin 


H  VN 
H  j 

that  is  to  say,  a  body  formed  from  neurin,  by  the  loss  of  three 
radicles  of  methyl  and  one  of  water. 

A  third  base  was  also  obtained  ;  it  was  soluble  in  alcohol  as 
platinic  salt,  giving  the  solution  a  brownish-red  colour,  and  on 
the  addition  of  much  ether  w^s  precipitated.  It  was  purified  by 
repeated  solution  in  alcohol  and  reprecipitation  by  ether.  Several 
grammes  of  this  body  which  was  precipitated  in  an  oily  state,  but 
became  solid  on  drying,  were  obtained.  It  was  dried  at  100°  C. 
and  analj^sed. 

Comjndatlon  of  Analij  es : 


--At  Wgts. 








3  070 


















leading  to  a  formula  C5H^4N20,HCl,PtCl4.  This  body,  so  ano- 
malous in  its  constitution,  has  probably  been  derived  from  neurin 
molecles  by  duplication  and  subsequent  decomposition.  Such  a 
condensation  is  observed  upon  the  neurin  molecles  under  the 

influence  of  oxidising  agents. 

C— 2 


i.  Third  Chemolysis  of  Kephalin  by  Barita. — The  process  was  the 
same  as  in  the  former  experiment.  The  platinum  salt  gave  on 
analysis  the  following  results  : 

Comjmtatlon  of  Analyses : 


H-At  Wgts. 

-^Pt  =  l. 












2  0 













=  (C,Hi3N0),(HCl),Pt01,. 

^.  Fourth  Chemolysis  of  Keyhalm  by  Barita. — This  experiment  was 
undertaken  upon  a  larger  amount  of  kephalin  than  the  previous 
ones.  The  kephalin  was  first  warmed  in  water,  whereby  it  swelled 
and  became  a  paste,  which  was  then  boiled  with  two  molecles  of 
BaH^Oo  in  the  ordinary  way. 

The  same  barium  salts  as  those  obtained  in  the  earlier  experi- 
ments were  again  found,  and  it  was  moreover  observed  that  one 
of  the  fatty  acids  contained  in  them  gave  the  purple  reaction, 
with  sugar  and  sulphuric  acid,  which  resembles  Pettenkofer's  test 
for  biliary  compounds. 

From  the  solution  drawn  off  from  the  barium  salts  of  the  fatty 
acids  the  excess  of  barium  was  removed  by  CO.,,  and  the  resulting 
filtrate  concentrated  by  evaporation,  and  then  treated  with  alcohol. 
The  glycerophosphate  of  barium  thus  obtained  was  converted  into 
lead  salt,  and  the  lead  salt  into  calcium  salt  (C3HX^aP0^3). 

Tlic  alcoholic  niother-li/juor  was  freed  from  alcohol  by  evaporation, 
and  the  resulting  solution  after  addition  of  nitric  acid  was  preci- 
pitated by  i)hospho-molybdic  acid,  and  the  product  decomposed 
by  hot  BaH.,02.  The  yellow  filtrate  freed  from  the  barium  which 
admitted  of  removal  by  CO.j,  did  yet  contain  barium  in  combina- 
tion. This  was  proved  by  coml)ustion  of  the  dried  salt  and 
analysis  of  the  residue. 

The  concentrated  solution  of  the  base  was  freed  from  Ba  by  an 
equivalent  amount  of  very  dilute  sulphuric  acid,  then  neutralised 
by  hydrochloric  acid,  and  preci})itated  after  concentration  by 
alcoholic  PtCl^.  The  i)recipitate  Avas  recrystallised  from  water, 
10  gr.  being  obtained  in  the  shaiie  of  crystallised  i)latcs.  The 
salt  was  dried  and  analysed. 


Computation  of  Analyses : 


-f-At  Wgts. 

-=-Pt  =  l. 

























=  {C,Hi3N0)„(HCl),PtCl,. 

The  alcoholic  mother-liquor  from  which  this  salt  had  been  pre- 
cipitated gave  by  precipitation  with  ether  a  quantity  of  the  fluid 
oily  salt,  the  analysis  of  which  has  been  given  in  a  former  para 
graph,  (C;^Hi^NoO)HClPtCl^,  but  it  was  very  small  in  amount. 

A  third  base  was  also  obtained  in  small  quantity  by  simple 
addition  of  much  nitric  acid  to  the  original  solution,  after  removal 
of  glycerophosphate,  and  before  precipitation  with  phospho- 
molybdic  acid,  and  which  gave  the  various  alkaloidal  tests. 

Fatty  Acids  produced  in  the  Chemolysis  of  Kephalin  from  Barium 
Salt  Insoluble  in  Ether. — The  barium  salt  insoluble  in  ether  was  de- 
composed, after  complete  extraction  with  ether  and  alcohol,  by 
boiling  with  hydrochloric  acid.  The  liberated  acid  which  solidified 
upon  cooling  was  dissolved  in  ether,  washed  with  water  so  long 
as  it  removed  colouring-matter,  and  the  ethereal  solution  was 
distilled  to  dryness.  The  acid  which  now  remained  was  dissolved 
in  warm  ammonia- water,  filtered  hot  and  precipitated  with  acetate 
of  lead.  The  lead  salt  after  being  dried  was  extracted  with  much 
ether,  which  efi'ected  a  separation  into  two  salts  : 
A  white  lead  salt  insoluble  in  ether. 
A  coloured  lead  salt  soluble  in  ether. 

The  Lead  Salt  Insoluble  in  Ether.  First  Preparation. — It  was 
decomposed  with  tartaric  acid  in  presence  of  ether  and  water, 
and  the  ethereal  solution  of  acid  after  washing  was  treated  with 
animal  charcoal,  which  clarified  and  partially  decolorised  it. 
The  acid  obtained  by  distillation  of  the  ether  was  repeatedly 
crystallised  from  watery  alcohol.  Finally  four  crystallisations 
were  obtained,  dried  by  fusion  for  some  time  at  105^  C,  and 
their  melting-points  determined.  No.  1  fused  at  68' ;  2,  at  66'  ; 
3,  at  62-5';  4,  at  63-5°  C.  These  preparations  were  united 
and  recrystalhsed  from  dilute  alcohol  with  animal  charcoal. 
They  finally  gave  one  large  crop  of  acid  melting  at  68'  C,  from 


the  mother-liquor  of  which  a  small  further  quantit}^  was  obtained, 
melting  at  66°  C.  It  w^as  stearic  acid,  mixed  with  a  small  quantity 
of  a  lower  homologue. 

Second  Preparation. — Another  portion  of  lead  salt  was  decom- 
l^osed  with  tartaric  acid  and  ether,  and  the  ether  distilled  to  a  low 
bulk.  On  cooling,  a  large  crop  of  nearly  white  crystals  Avas 
obtained.  After  separation  from  the  highly  coloured  mother- 
liquor  l)y  filtration  and  pressing,  the  acid  was  twice  recrystallised 
from  dilute  sjnrit  with  animal  charcoal.  There  was  thus  obtained 
a  perfectly  colourless  acid,  having  a  fusion-point  of  70'  C.  This 
was  dried  for  analysis  by  fusion  at  110°  C,  after  which  treatment 
its  fusion-point  was  found  still  the  same.  Analysis  led  to  the 
empirical  formula  CjgHgyO^,,  which  is  that  of  stearic  acid.  This 
acid  has  the  same  melting-point,  microscopic  appearance,  and 
other  physical  characteristics  as  stearic  acid.  A  portion  of  it 
dissolved  in  dilute  ammonia  gave  a  salt  w^hich  dissolved  perfectly 
on  heating,  almost  completely  separated  in  crystals  on  cooling,  and 
otherwise  exactly  resembled  stearate  of  ammonium  prepared  from 
pure  stearic  acid. 

Third  Preparation. — Obtained  by  chemolysis  with  hydrochloric 
acid.  The  insoluble  in  ether  lead  salt,  from  insoluble  in  ether 
barium  salt  obtained  in  this  chemolysis  (' Keport,'  1876,  p.  118), 
was  examined  as  to  its  identity  with  the  analogous  salt  obtained 
in  the  barita  chemolysis.  It  was  decomposed  with  tartaric  acid 
in  presence  of  ether,  and  the  ethereal  solution  was  distilled,  and 
when  sufficiently  concentrated  was  allowed  to  crystallise.  The 
crystals,  purified  by  recrystallization  from  watery  alcohol  with  the 
aid  of  animal  charcoal,  gave  a  white  product,  which  fused  at 
69°  C.  and  was  analysed.  In  all  respects  it  was  identical  with 
stearic  acid. 

Lead  Salt  Soluble  in  Ether. — The  clear  ether  solution  was  distilled 
to  dryness,  again  dissolved  in  ether,  decanted  from  matter  rendered 
insoluble,  and  treated  with  a  concentrated  solution  of  tartaric  acid. 
The  ethereal  solution  of  the  acid  free  from  lead  gave  on  evapora- 
tion a  viscid  mass  which,  being  dissolved  in  ammonia  and  pre- 
cipitated with  barium  chloride,  gave  a  viscous  barium  salt.  This 
yielded  to  boiling  alcohol  a  small  amount  of  a  salt  which  was 
analysed.  It  contained  19-65  per  cent,  of  barium.  This  body 
requires  much  further  study. 

Barium  Salt  Soluble  in  Ether,  Keplialate.    Product  of  the  first 


Clismolysis. — This  salt  dissolved  in  ether  with  a  red-brown  colour, 
from  which  it  was  impossible  to  free  it  by  any  process  whatever. 
To  try  whether  this  colour  were  due  to  oxidation  caused  by  contact 
with  the  air,  some  of  the  free  acid  was  enclosed  in  a  tube  with  a 
measured  volume  of  oxigen  gas,  but  no  absorption  was  observed. 
It  is  therefore  clear  that  any  oxidation  must  take  place  in 
ethereal  solution,  and  in  that  case  must  be  ascribed  to  the  per- 
oxide of  hydrogen  formed  by  the  ether.  The  red-brown  colour 
appears  to  be  proper  to  the  acid  and  its  salts.  To  ascertain 
whether  the  soluble  in  ether  barium  salt  contained  more  than 
one  acid,  it  was  decomposed  with  tartaric  acid  in  presence  of 
ether,  and  the  liberated  acid  obtained  upon  distillation  to  dryness 
was  dissolved  in  ammonia  and  precipitated  with  acetate  of  lead. 
The  lead  salt  was  dissolved  in  ether,  and  fractionally  precipitated 
in  three  portions  by  successive  additions  of  alcohol.  The  fractions 
were  analysed,  and  gave  38-07,  38*48,  and  36-39  per  cent.  lead. 

It  is  therefore  probable  that  the  soluble  barita  salt  mainly 
consists  of  one  acid  only.  The  following  attempt  was  made  to 
obtain  it  in  a  state  fit  for  analysis. 

After  the  barium  salt  had  been  exhausted  with  boiling  alcohol 
it  was  dissolved  in  ether,  and  the  intensely  coloured  solution  pre- 
cipitated by  alcohol ;  the  precipitate  was  redissolved  in  ether  and 
again  precipitated.  The  mother-liquors  removed  no  colouring- 
matter.  The  compound  was  next  decomposed  by  tartaric  acid, 
the  free  acid  dissolved  in  ether ;  the  solution  was  distilled  to  dry- 
ness, and  the  residue  extracted  with  absolute  alcohol.  The 
solution  thus  obtained  was  treated  w^ith .  ammonia  in  excess,  and 
the  filtered  clear  soap  solution  precipitated  with  acetate  of  barium. 
The  precipitated  salt  was  analysed. 


-^At.  Wgts. 















13-673  > 



These  data  lead  to  a  formula  of  about  Ba(Cj^^H3^03)2. 

/.  Product  of  the  Secondary  Cliemdysis  with  Barita  a7id  Caustic  Soda 
in  Succession. — On  account  of  these  unsatisfactory  results,  and  from 
a  fear  that  the  salt  might  contain  traces  of  undecomposed  kephalin, 
it  was  again  submitted  to  a  barita  chemolysis  ;  but  as  it  agglo- 
merated into  large  masses,  into  the  interior  of  which  the  barita  had 



little  access,  it  was  decomposed  by  treatment  with  hydrochloric  acid 
and  water.  The  free  acid  after  solution  in  ether  and  distillation 
to  dryness  was  dissolved  in  warm  dilute  caustic  soda,  a  large 
excess  of  soda  added,  and  the  whole  boiled  seven  or  eight  hours 
a  day  for  several  successive  days.  There  was  great  frothing 
which  could  not  be  prevented,  but  any  loss  was  obviated  by 
allowing  the  froth  to  issue  from  the  wide  beak  of  the  platinum 
retort  employed,  into  a  large  beaker  where  it  slowly  subsided. 
From  time  to  time  the  fluid  which  collected  was  returned  to  the 
retort.  At  the  end  there  was  obtained  a  brown  turbid  solution 
showing  on  agitation  the  silky  clouds  common  in  soap  solutions. 
It  was  filtered  as  clear  as  possible  by  the  vacuum  method,  and 
the  solution  precipitated  with  acetate  of  lead.  The  voluminous 
precipitate,  after  washing  and  drying,  was  extracted  with  ether, 
when  it  mostly  dissolved,  leaving,  however,  an  amount  of  insoluble 
salt,  probably  stearate.  The  clear  ether  solution  was  treated  with 
a  concentrated  solution  of  tartaric  acid,  the  ethereal  solution 
of  acid  separated  from  tartrate  of  lead,  distilled  to  dryness,  dis- 
solved in  a  minimum  of  caustic  soda,  and  precipitated  with  barium 
chloride.  The  barium  precipitate  was  washed,  dried,  suspended 
in  ether,  and  a  solution  was  separated  by  decantation  and  filtra- 
tion from  a  white  insoluble  salt  which  appeared  much  swollen  in 
ether.  The  insoluble  salt  was  analysed,  but  did  not  lead  to  any 
formula.  The  ethereal  solution  after  concentration  was  preci- 
pitated by  addition  of  a  minimum  of  absolute  alcohol  and  the 
precipitate  analysed. 


-^At.  Wg-ts. 

H-Ba  1 

















leading  to  the  formula  Ba(Cj^H3Q03)^. 

The  filtrate  on  examination  was  found  to  contain  a  small 
quantity  of  a  kephalin-like  body.  The  precipitate  was  therefore 
again  dissolved  and  reprecipitated  by  a  little  alcohol,  washed  with 
absolute  alcohol,  and  analysed  : 


-^At.  Wgts. 

-f-Ba  =  l 

















'pointing  to  an 

empirical  formula  Ba(Cj;Hos.O;.)j. 


The  acid  obtained  by  decomposing  this  salt  with  hydrochloric 
acid  is  a  dark-coloured  viscid  oil  at  the  ordinary  temperature, 
which  is  wholly  soluble  in  alcohol,  the  solution  not  being  de- 
colorised by  even  large  quantities  of  animal  charcoal.  On 
evaporation,  or  on  addition  of  water,  the  acid  separates  from  the 
alcohol  in  brown  oily  drops.  On  fusion  with  potash,  no  solid  acid 
is  obtained,  but  a  brown  acid  which  has  all  the  properties  of  the 
original  body,  and  gives  a  barium  salt  which  contains  about  19 
per  cent,  of  barium,  and  is  soluble  in  ether. 

Thus  this  acid  gives  none  of  the  ordinary  physical  guarantees  of 
purity,  but  the  pertinacity  with  which  it  retains  its  composition 
and  properties  under  the  most  varied  and  severe  treatment,  points 
distinctly  to  its  chemical  unity,  while  the  quantity  in  which  it 
occurs  shows  its  radicle  to  be  a  principal  ingredient  in  the 
kephalin  molecle. 

yt.  Theory  of  the  Chemical  Constitution  of  the  Kephalins. — Accord- 
ing to  the  theories  hitherto  in  vogue,  kephalin  may  be  regarded, 
considering  its  elementary  composition  and  the  products  of  its 
chemolysis,  as  a  body  in  which  two  hydroxyls  of  the  glycerin 
molecle  are  replaced  by  fatty  acids,  and  in  which  the  third 
hydroxyl  is  replaced  by  phosphoryl,  which  latter  in  its  turn  has 
one  hydroxyl  replaced  by  an  ammonium  base,  thus  : 

(  Fatty  acid  A. 
C3H5  \  Fatty  acid  B  or  C. 
( H0(0P0)C5Hi,N0. 

The  whole  of  the  phosphorus  is  apparently  contained  in  the 
radicle  of  glycerophosphoric  acid,  and  in  no  other  form.  This 
body  is  first  obtained  on  chemolysis,  but  being  somewhat  un- 
stable, it  is  not  difficult  in  the  presence  of  bases  to  decompose  it 
further  into  glycerin  and  phosphate  of  the  base  used. 

The  whole  of  the  nitrogen  appears  to  be  present  as  neurin ;  the 
other  bases  which  have  been  obtained  being  probably  derived 
from  neurin  by  secondary  changes.  This  secondary  decomposition 
would  explain  why  the  amount  of  the  neurin  obtained  from  a 
given  weight  of  kephalin  is  less,  sometimes  much  less,  than  the 
amount  which  theory  would  lead  us  to  expect. 

Of  the  fatty  acids  contained  in  kephalin,  various  barium,  lead, 
and  magnesium  salts  have  been  examined  and  analysed.  It  is 
highly  probable  that  the  acid  contained  in  the  main  soluble  in 
ether,  barium,  or  lead  salt,  namely  kejjhalic  acid,  belongs  to  a 


series  of  acids  containing  at  least  one  atom  of  oxigen  more  than 
the  ordinary  fatty  acids.  It  is  this  fatty  acid  which  impresses 
its  pecuHar  character  upon  all  the  kephalins,  and  without  its 
presence  a  phosphorised  body  constituted  as  above  assumed  does 
not  seem  to  exhibit  the  properties  of  a  kephalin.  But  the 
kephalins  may  vary  as  regards  the  second  acid  ;  in  the  principal 
kephalin  this  acid  is  stearic;  but  in  certain  kephalins  which  occur 
in  subordinate  quantity  the  second  acid  is  either  an  acid  of  lower 
fusing-point  than,  though  probably  homologous  with,  stearic  acid, 
or  an  acid  not  homologous  with  stearic,  and  giving  a  lead  com- 
pound soluble  in  ether.  The  constitutional  formula  of  the 
jH'incipal  kephalin,  or  lephalo-stearo-neuro-glyceropliosphate  would 
thus  be  the  following  : 

A  kephalin  with  palmityl,  C^^Hg^O.,,  in  place  of  stearyl  would  have 
the  summary  formula  C4jH^-NP0i^ ;  a  kephalin  with  margaryl, 
Cj^HygO^,  would  be  C^^H^c^NPOg.  If  there  were  several  homolo- 
gous kephalic  acids  such  as  some  analyses  seem  to  indicate,  then 
for  a  kephalyl  of  formula  Cj^Hy^^Oy  combined  with  either  stearyl, 
or  margaryl,  or  palmityl,  the  foregoing  formulae  w^ould  have  to  be 
increased  by  CH^  each,  so  that  the  most  complicated  kephalin 
might  contain  44  atoms  of  carbon. 

It  will  be  seen  that  none  of  these  hypotheses  explain  either  the 
deficiency  of  hydrogen  or  the  excess  of  oxigen  in  the  various 
kephalins  and  their  compounds  which  have  been  analysed.  This 
discrepancy  can  only  be  eliminated  by  further  researches  carried 
on  by  the  light  of  those  given  in  the  foregoing. 

We  have  considered  the  kephalins  as  glycerides,  in  which  three 
hydroxyls  are  substituted.  It  is,  however,  evident  from  the  con- 
stitution of  sjiliingomyelin,  to  be  described  l)elow,  and  generalised 
in  the  introduction,  that  they  may  also  be  considered  as  plm- 
jyJiatides,  or  bodies  held  together  by  phosphoric  acid,  thus  : 

Phusphoik  Acid.  Keplialhi. 

the  neuryl  re})lacing  an  hydroxyl  in  glyceryl,  and  being  the 


I  HO 
OP  '  HO  OP 
I  HO 


radicle  which  is  the  earliest  to  be  detached  by  chemolysis.  On 
this  assumption  the  kephalophosijhoric  acid  above  described  would 
have  the  formulae  : 

OP    C,3H3A  -CasH.oPO,. 

3.  Paramyelin  :  ITS  Isolation,  Analysis,  and  Compounds. 

Pararmjeliti  is  a  nitrogenised  phosphatide,  and  is  in  the  first 
stage  diagnosed  and  separated  by  the  solubility  of  its  cadmium 
chloride  compound  in  hot  benzol,  from  which  solution,  filtered 
boiling,  it  is  deposited  on  cooling.  In  this  condition  the  com- 
pound is  very  voluminous  and  gelatinous,  and  is  only  with  ver}^ 
great  difficulty  separated  from  the  lecithin  cadmium  chloride 
compound  which  remains  in  solution  in  the  cold  benzol.  The 
mechanical  aids  to  this  separation  are  two  in  number ;  one  the 
cylindrical  vacuum  filter  described,  the  other  the  use  of  very 
large  volumes  of  benzol  for  the  extraction  of  the  soluble  com- 
pound, the  removal  of  the  solution  by  the  syphon  from  above 
the  deposit,  and  very  frequent  repetition  of  this  process.  In  this 
i:)rocess  the  large  volumes  of  benzol  require  many  distillations  for 
recovery ;  the  deposition  of  the  paramyelin  compound  requires 
time.  But  when  once  obtained  free  from  matters  soluble  in  cold 
benzol,  the  compound  behaves  with  great  precision.  It  is,  whilst 
moist  with  benzol,  washed  with  spirit,  which  dissolves  any  colour- 
ing-matter, and  it  is  well  to  repeat  this  washing  by  shaking  the 
comjDound  in  a  bottle,  etc.,  until  the  supernatant  spirit  is  colour- 
less. The  compound  thus  obtained  is  soluble  in  boiling  spirit, 
and  deposited  on  cooling  ;  it  is  easily  decomposed  by  hydrothion 
in  sj)irit,  and  the  hot  solution  yields  on  cooling  white  crystallised 
paramyelin  hydrochlorate.  This  by  re -crystallisation  or  washing 
loses  its  acid  easily,  and  free  crystallised  paramyelin  remains. 

A  specimen  of  paramyelin  caclm'iuin  chloride  compound  obtained 
from  the  extracts  of  human  brain  by  the  process  described  under 
lecithin,  but  without  the  previous  purification  by  lead,  soluble  in 
boiling,  insoluble  in  cold  benzol,  dried  at  100°,  gave  on  analysis 
13-70  per  cent.  Cd,  3-59  per  cent.  P,  9-68  per  cent.  CI  (this 
requires  15-27  per  cent.  Cd,  whereas  only  13*70  per  cent.  Cd  were 
found,  total  CdClg  calculated  from  CI  =  24-95  per  cent.),  1-69  per 
cent.  N,  47-19  per  cent.  C,  and  7-94  per  cent.  H. 


These  data  exhibit  the  following  ratios  : 

P  :  N  =  1  :  1-06 
P  :  CdCl,  =  1  :  1-20 
N  :  CdCi;  =  1  :  M3 

If  CdCl^  be  calculated  from  CI  =  24-95  \ 

then  the  organic  molecle  is  =  75-05  j 

If  CdCl^  be  calculated  from  Cd  =  22-39  ) 

then  the  organic  molecle  is  =  77-61  } 

=  100 
=  100 

These  relations  thus  show  a  slight  excess  of  nitrogen  over  the 
relation  N  :  P  =  1  :  1,  and  a  more  important  excess  of  cadmium 
chloride  over  the  presumable  relation  N  :  CdCl.,  =  1:1.  Bat 
considering  that  the  compound  is  a  first  product,  the  relations 
are  satisfactory,  as  showing  the  firmness  of  the  compound.  In 
the  following  I  give  a  comparison  of  this  salt  with  the  paramyelin 
salt  from  ox  first  described. 

Summary  of  Hitman  Paramyelin     Summary  of  Ox  Paramyelin 
Cadmium  Chloride.  ,        Cadmium  Chloride. 

Percents.  Percents. 

C    47-19  N  C  49-288 

H  8-299 
75-05  N     1-598  V 78-725 

H  7-94) 

N  1-69  >-7 

P  3-59  \ 

O  14-64 

(Calcd.)  Cd  15-27  1  (Calcd.)  Cd  13-020  ) 

(Found)  CI  9-68  /  (Found)  CI      -255  )  ^'"^ 

P  3-396 
0  16-144 

Computation  of  the  Organic  Moleclcs  of  these  Salts. 

Percents  ^  by  At.  Ws.  -r-  P  =  l.  Percents.  -^  At,  Ws.  -J-  P  =  l. 

408    C    62-87      5-239    34  C  62-607     5-217    37-5  456 

68    H  10-58    10-58      68  H  10-541   10-541    75-8  76 

14    N     2-25      0-160      1-03  N  2-029     0-144      1-0  14 

31    P     4-78      0-154      1  P  4-313     0-139      1-0  31 

l-_8    0   19-50      1-24       8  O  20  510     1-281      9*2  144 

649  '  721 

The  percentages  of  carbon  and  hydrogen  are  practically  iden- 
tical in  both  organic  molecles.  Other  data  show  distinctly  that 
the  salt  is  not,  and  does  not  contain,  either  amidomyelin  or 
sphingomyelin.  The  absence  of  lecithin  follows  from  the  solu- 
bility in  cold  benzol  of  its  cadmium  chloride  compound.  The 
data,  however,  do  not  show  that  the  compound  is  unitary,  and 


does  not  contain  two  or  more  similar  principles  (paramyelins). 
They  also  do  not  sho  w  the  exact  composition  of  the  organic 
molecle,  for,  as  we  know  from  a  vast  amount  of  experience,  this 
can  only  be  ascertained  with  the  aid  of  several  compounds,  and 
of  the  decomposition  products  of  the  principle  under  the  influence 
of  chemolytic  agents.  For  the  study  of  these  relations  the  past 
has  afforded  no  time  or  opportunity,  and  it  must  therefore  be  left 
to  the  future. 

Preparation  of  Free  Parainyelin  from  the  CaJmiam  Chloride 

The  CdCU  salt  of  human  paramyelin  was  suspended  in  spirit, 
and  treated  with  H2S,  at  first  at  the  ordinary  temperature,  later 
on  at  75°  in  the  water-bath,  until  it  was  completely  decomposed. 
The  filtrate,  on  standing  and  cooling,  deposited  white  crystallised 
paramyelin.  The  crystals  were  rhombic  and  hexagonal  plates  of 
microscopic  dimensions.  They  were  collected  on  a  filter,  washed, 
pressed,  recrystallised  from  spirit  to  remove  a  trace  of  colour  and 
the  rest  of  the  hydrochloric  acid,  and  dried  in  vacuo.  On  analysis 
they  gave  4-31  per  cent.  P,  and  2*06  per  cent.  N. 

These  two  analyses  show  that  N  :  P  =  l-00  :  1-00. 

The  atomic  weight  of  j^aramyelin  as  deduced  from  the  per- 
centage of  phosphorus  is  688 ;  as  deduced  from  nitrogen,  666  ; 
mean,  677  (for  the  free  body).  The  atomic  weight  of  paramyelin 
(human)  as  deduced  from  the  organic  molecle  in  the  CdCl.,  salt  is 
649 ;  that  for  ox  paramyelin  combined  in  the  same  manner  is  721 ; 
mean  680.    These  two  means  are  practically  identical. 

The  question  now  arises  whether  this  phosphatide  contains 
glycerol  or  not,  neurin  or  not ;  these  questions  can  be  answered 
by  chemolysis  only. 

Paramyelin  Cadmium  Chloride  (Ox). — C3gP^-IS['P09,CdC1.2. 
From  Ox-huttery  after  Kephaloidin. 
"When  the  buttery  matter  dissolved  in  ether  had  been  precipi- 
tated by  alcohol  and  the  kephaloidin  been  removed,  the  mother- 
liquor  on  standing  deposited  some  secondary  kephaloidin  and 
cholesterin.  These  were  filtered  off* ;  the  liquid  was  precipitated 
with  CdCl2 ;  the  precipitate  was  washed  with  alcohol,  and  pressed  ; 
it  was  next  extracted  with  ether  (which  dissolved  a  small  quantity 
of  kephaloidin  CdCU)  until  pure,  dried,  and  analysed.  The  result 
of  the  analyses  showed  that  the  body  was  a  CdCl.,  compound. 


The  organic  molecle  amounted  to  77 "49  per  cent,;  the  CdCl^  to 
22-51  per  cent. 

Treatment  nitli  Benzol. — It  was  found  that  the  compound  was 
entirely  soluble  in  boiling  benzol,  and  deposited  a  portion  on 
cooling  which  was  white  and  voluminous.  Another  portion  re- 
mained dissolved  in  the  cold  benzol.  The  deposit  was  isolated  by 
filtration,  dissolved  once  more  in  boiling  benzol,  and  was  deposited 
as  a  swelled  gelatinous  mass  ;  from  this  benzol  was  drained  by 
blotting-paper,  and  the  residue  was  dried. 

Faramyelin  Cadmium  Chloride^  Q.^fi^^VOc^.C^GV^. — Insoluble  in 
cold  benzol.    The  analyses  were  carried  out  in  the  usual  manner, 
but  the  Cd  was  not  estimated. 
Sv.mmary : 













)Cd  (13-020) 





21  275 


Computation  of  Organic  Molecle  : 

Percents.         -4-by  At.  Wgts.  -^byP  =  l. 

C       62-607              5-217  37-5 

H      10-541            10-541  75-8 

N        2-029             0-144  "  I'O 

P        4-313             0-139  1-0 

O       20-510              1-281  9-2 


The  formula  CygHn^NPOg  gives  an  atomic  weight  of  720,  but 
the  atomic  weight  calculated  from  the  CdCl^  is  only  677 ;  720  +  183 
(CdCl2)  =  903  requires  20-2  per  cent.  CdCl^.  There  is,  therefore, 
still  an  irrationality  between  the  chloride  and  the  organic  molecle, 
in  the  sense  of  the  metallic  salt  being  in  excess. 

4.  Myelin  :  its  Isolation,  Analysis  and  Compounds. 

General  Definition  of  Myelin. — The  leading  features  of  the  prin- 
ciple here  to  be  described  will  distinguish  it  with  great  precision 
from  all  similar  matters.    When  freshly  obtained  it  is  white  like 

V*^^.  ffOaV^OMEH 


bleached  ivory,  but  when  kept  for  some  time  it  becomes  a  little 
yellowish  and  waxy.  It  crystallises,  from  ether  or  absolute 
alcohol  solution  on  slow  evaporation,  in  curved  needles  aud  scales 
of  a  rhombic  ovoid  shape,  which  are  well  seen  under  the  micro- 
scope with  a  power  of  x  400.  When  it  is  in  minute  crystals  it 
remains  powdery  even  after  drying,  but  when  drying  in  body 
after  deposition  from  alcohol  and  washing  by  ether,  it  becomes 
transparent  and  waxy,  cuts  like  dry  walnut  kernel,  and  when  dry 
can  be  powdered.  The  powder  is  perfectly  white.  It  swells  and 
emulges  with  water,  particularly  on  the  application  of  heat,  in  the 
manner  defined  for  all  phosphorised  cerebral  principles.  The 
solution  iridesces  bluish-white  from  polarisation  of  the  minute 
particles.  This  solution  gives  the  reactions  to  be  described.  It 
dissolves  in  hot  alcohol  abundantly,  and  is  deposited  on  cooling  in 
white  tufts,  granules,  and  masses  of  peculiar  appearance,  and  on 
slow  evaporation  in  crystalline  needles.  The  alcohol  retains  little 
myelin  in  solution  when  cold,  and  gives  no  precipitates  with 
CdClg  and  PtCl^.  It  dissolves  very  sparingly  in  hot  ether,  and 
is  almost  immediately  deposited  from  this  solution  when  its  tem- 
perature sinks.  It  is  less  soluble  in  cold  ether  than  in  boiling. 
It  contains  more  than  three  per  cent,  of  phosphorus.  With  Pb 
acetate  and  ammonia  it  gives  a  white  salt,  which  is  insoluble  in 
alcohol  and  ether,  and  contains  an  atom  of  lead.  Myelin  is  conse- 
quently a  dibasic  acid. 

Modes  of  oUaining  Myelin. — It  can  be  obtained  directly,  without 
the  intervention  of  precipitants,  from  the  cold  alcohol  extracts  of 
white  matter,  by  concentration  and  cooling,  redissolving  the  pre- 
cipitate, and  letting  the  solution  stand  for  a  long  time  in  the  cold, 
when  myelin  is  deposited  crystalline.  After  isolation  it  has  to  be 
washed  with  a  little  ether,  combined  with  lead,  and  freed  from 
sphingomyelin  by  boiling  spirit. 

The  ether  extracts  of  white  matter  may  be  precipitated  by 
alcohol,  the  precipitate  emulged  with  water,  treated  with  lead 
acetate  and  ammonia,  washed,  and  extracted  with  hot  alcohol  and 
ether  in  succession,  when  ultimately  white  myelin  lead,  of  the  for- 
mula to  be  given,  remains  insoluble  in  these  agents.  The  lead 
salt  decomposed  by  in  water,  and  the  precipitate  extracted 
with  hot  alcohol,  yields  white  myelin ;  or  the  lead  compound  may 
be  decomposed  in  hot  spirit  by  hydrogen  sulphide. 

Differences  and  Sejmration  from  other  Cerebral  Prhiciples. — Myelin 


can  be  separated  from  kephalin  and  kephaloidin  and  allied  bodies 
by  the  operator  using  the  peculiarity  of  its  being  veiij  little  soluble 
in  cold  ether,  in  which  these  bodies  and  their  compounds  are  easily 
solul)le.  The  solutions  should  always  be  exposed  to  a  very  power- 
ful freezing  mixture,  and  filtered  through  a  filter  and  funnel  sur- 
rounded with  freezing  mixture.  From  lecithin  myelin  can  be 
separated  by  the  lead  process. 

Myelin  can  be  separated  from  the  cerehrosides  by  much  boiling 
alcohol,  in  which  both  are  largely  soluble,  but  the  cerehrosides  are 
almost  insoluble  in  cold  alcohol,  in  which,  therefore,  myelin  would 
remain  dissolved  on  cooling  more  readily.  But  the  lead  process 
is  preferable,  and  necessary  in  any  case  as  a  means  of  precipitation. 

An  absolute  separation  of  myelin  from  the  other  phosphorised 
principles  is  best  effected  by  the  processes  employing  lead  acetate, 
and  from  cerehrosides  (as  obtained  by  alcohol  process)  by  ex- 
traction with  boiling  alcohol  and  separation  after  cooling. 

No  phosphatide,  however  similar  in  bearing  to  myelin,  should 
be  assumed  to  be  myelin  before  it  has  been  in  combination  with 
lead,  and  been  found  insoluble  as  lead  salt  in  boiling  alcohol  and 
in  ether. 

M//elin  Lead.—C^QR^.^'Ph^VO^^y  The  ether-solution  from 
white  matter,  after  exhaustion  by  freezing,  was  precipitated  by 
alcohol ;  the  bulky  precipitate  was  filtered,  washed,  and  dried 
in  vacuo,  and  during  this  process  repeatedly  pounded  in  a  mortar. 
It  was  now  swelled  in  water,  and  subjected  to  dialysis  ;  it 
formed  a  thick,  slimy,  gummy  or  starch-like  emulsion,  in  which 
many  small  crystals  of  cholesterin  formed.  The  addition  of 
w^atery  Pb  acetate  produced  a  dense  curd,  which  separated  easily 
from  fluid  ;  it  was  placed  on  a  cloth  filter  and  allowed  to  drain 
away  its  mother-liquor.  The  precipitate  was  placed  in  alcohol 
and  warmed,  whereby  little  else  but  water  was  extracted  (one 
litre  alcohol  left  on  evaporation  to  dryness  a  little  brown  matter). 
More  warm  strong  alcohol  noAv  extracted  much  cholesterin.  Hot 
boiling  absolute  alcohol  extracted  7nuch  cholesterin  and  a  little 
yellow  smeary  lead  salt.  The  insoluble  part  was  soft,  waxy,  but 
on  cooling  granular.  It  was  now  placed  in  ether,  whereby  a 
yellowish  fluorescent  lead  salt  of  kephalin  was  extracted.  This 
latter  salt  was  i)recii)itated  by  absolute  alcohol,  deposited  as  a 
yellowish  oily  body,  wdiich  l)ecame  hard  on  standing.  This  has 
been  treated  under  kephalin.    A  ichite  pulverulent  salt  remained 


insoluble  in  the  ether,  was  thoroughly  washed  with  ether  on  the 
filter,  also  shaken  with  ether  in  a  bottle,  and  again  washed  on 
the  filter.  It  shrunk  much  on  drying.    It  was  insoluble  in  benzol. 

Substance  dried  at  100^  C.  gave,  on  analysis,  data  which  are 
arranged  in  the  following  summary  of  analyses  and  theories  : 


-^-byAt.  Wgts. 

-j-byPb  =  l. 

-f-byX  =  l. 

-^bYP  = 

C  50-88 





H  7-89 





Pb  19-76 





N  1-44 





P  3-28 





0  16-75 






The  organic  body  in  the  salt  =  100-19-76  =  80-24. 
Percentages  of  elements  found  in  organic  body  and  theories  : 

-^by  At.  Wgts. 

by  X  =  l. 

H-by  P-1. 



























There  are  thus  arguments  at  hand  for  atomic  weights  with 
from  40  atoms  to  44  atoms  of  carbon  ;  but  the  combined  metals 
and  salts  are  perhaps  less  to  be  relied  upon  for  atomic  weight 
determinations  of  the  phosphorised  principles  than  the  consti- 
tutional elements  P  and  X.  These  latter,  therefore,  prevail  in 
my  opinion  as  determinants,  particularly  as  they  agree  well  with 
each  other.  I  therefore  accept  C^^jH-.^XPO^q  as  the  formula  of 
the  body  combined  with  lead,  and  adding  2H  in  the  place  of  Pb, 
the  formula  of  the  free  body  will  be  C^,3H--XP0j,). 

Theory  of 



At.  Wgts. 


40  C 




75  H 




1  X 




1  P 




10  0 







Decomposition  of  PI  Salt  hj  H.^S. — A  portion  was  decomposed  by 
H^S  while  suspended  in  ether.  The  ethereal  filtrate  from  the 
PbS  deposited  a  white  flaky  matter  on  being  shaken,  which  in- 
creased in  quantity  on  standing.  It  was  allowed  to  go  to  dryness 
spontaneously,  and  left  an  abundant  white  residue,  which  was 
soft,  and  smelled  peculiarly.  It  fused  above  100°,  was  perfectly 
fused  about  125°  to  130°,  and  on  cooling  was  quite  solid  again  at 
100°.  On  being  heated  further  it  cracked  and  spirted,  then  gave 
off  strong-smelling  fumes,  burnt  with  a  white  luminous  flame, 
and  left  a  charcoal  difficult  to  incinerate.  Fused  with  nitre  and 
soda,  and  the  fused  mass  dissolved  in  HNO3,  the  tests  for  lead 
gave  negative  results,  but  the  tests  for  P2O3  gave  evidence  of 
abundance  ;  so  that  the  H^S  treatment  removed  all  the  lead. 

The  supposed  PbS,  when  heated,  fused,  and  gave  off  car- 
bonaceous vapours,  and  behaved  in  such  a  manner  as  to  indicate 
that  it  did  yet  contain  much  organic  matter. 

The  entire  quantity  of  finely-powdered  lead  salt  was  now  placed 
in  absolute  alcohol,  and  decomposed  with  H^S  while  being  heated 
in  a  water-bath,  filtered  hot,  and  extracted  with  hot  alcohol  as 
often  as  was  necessary  to  effect  complete  exhaustion.  The  alcohol 
extract,  on  cooling,  deposited  a  crystalline  mass.  This  was  re- 
crj^stallised  from  absolute  alcohol,  when  a  tendency  to  stearoco- 
notise  became  evident  in  the  deposit ;  but  all  ultimately  dissolved 
with  the  aid  of  hot  ether,  and  the  first  purest  portion  of  crystals 
was  analysed.    Dried  at  100°  C,  they  became  coloured  on  surface. 

Summanj  and  Computation  : 

Percents.  -^byAt.  Wgts.  -f-byP  =  l. 

C    62-651              5-221  39-0 

H    10-340            10-340  77-1 

N     2-000             0-142  1- 

P      4-170             0-134  1- 

O    20-829             1-301  9-7 

The  isolated  myelin  thus  exhibits  the  formula  C3C)HH.^NP0y. 


1.  Amidomyelin:  its  Isolation,  Analysts,  and  Compounds. 

Amidomyelin  is  met  with  in  certain  precipitates  obtained  from 
brain  extracts  by  the  agency  of  cadmium  and  platinum  chloride. 
These  precipitates  are,  as  regards  crystalline  appearance  and  bearing 


towards  solvents,  seemingly  homogeneous ;  but  on  elementary 
analj^sis  they  show  an  irrationality  between  the  phosphorus  and 
nitrogen,  which  in  not  a  few  cases  assumes  the  proportion  of 
P  :  N  =  2  :  3,  all  other  elements  being  present  in  nearly  the  same 
average  atomic  proportions  as  those  in  which  they  are  found  in 
phosphatides  in  which  P  :  N  =  1  :  1.  I  explain  these  variations 
of  the  nitrogen  as  due  to  the  presence  of  a  compound  in  which 
P  :  N  =  1  :  2.  After  the  discovery  of  ajjomyelin,  and  lately  of 
sjjhingomyelin,  in  both  of  which  principles  P  :  N  =  1  :  2,  I  isolated 
amidomyelin  by  the  which  have  already  been  partially 
described  under  the  chapter  relating  to  lecithin.  These  processes 
had  to  be  guided  by  incessant  quantitative  elementary  analysis  by 
which  to  control  the  progress  and  direction  of  the  purification  of 
the  principle  sought  to  be  isolated.  It  was  found  that  differentiat- 
ing solvents  and  combinants  were  the  principal  means  for  effecting 
this  isolation  and  purification,  and  that  so-called  fractional  crystal- 
lisation and  recrystallisation  were  only  of  subordinate  value.  No 
diagnostic  value  was  found  to  be  attached  to  so-called  uniform 
crystalline  or  crystallised  appearances  ;  for  a  great  number  of 
chemically  similar  or  dissimilar  bodies  would  crystallise  in  such  a 
manner  as  to  make  the  impression  of  homogeneity  upon  the  eye, 
while  their  diversity  could  be  quickly  and  incontrovertibly  proved 
by  appropriate  chemical  reagents. 

Process  for  the  Isolation  of  Amidomyelin. 

The  buttery  matter  from  human  or  bovine  brains  is  dissolved 
in  hot  spirit,  and  to  the  solution  an  ammoniacal  solution  in  spirit 
of  lead  acetate  is  added  as  long  as  a  precipitate  is  produced. 
This  precipitate  is  removed  by  filtration  on  a  funnel  heated  by 
steam.  It  contains  kephaloidin  and  myelin  as  lead  salts  ;  lead 
salts  of  phosphatides,  free  from  nitrogen,  and  some  lead  salts  of 
cerebrinacides,  the  latter  in  small  quantity.  The  filtrate  deposits 
on  cooling  a  mixture  of  cholesterin  with  lead  salts,  particularly  of 
myelin  and  cerebrinacides,  and  other  phosphatides  in  the  free 
state,  amongst  them  some  amidomj^elin.  The  clear  filtrate  is 
mixed  with  a  spirituous  solution  of  cadmium  chloride  as  long  as 
a  precipitate  is  produced  :  an  excess  of  cadmium  solution  is  then 
added,  and  the  mixture  is  allowed  to  stand  for  the  precipitate  to 
contract  and  settle. 

The  mixture  of  cholesterin,  lead  salts,  and  other  phosphatides, 



is  again  boiled  with  spirit  and  allowed  to  become  cool  without 
haying  been  filtered  while  hot.  The  liquid  is  filtered  from  the 
insoluble  and  crystallised  matter,  and  in  its  turn  treated  with 
cadmium  chloride  solution  in  the  manner  stated  for  the  first 
solution.  In  this  manner  the  cholesterin  and  lead  salts  mixture 
is  extracted  with  spirit  as  long  as  the  mother-liquors  give  precipi- 
tates with  cadmium  chloride.  The  last  extracts  are  the  richest 
in  amidomyelin.  The  cadmium  chloride  precipitates  are  all 
united,  washed  with  spirit  by  decantation  until  the  washings  are 
colourless,  exhausted  with  ether  by  decantation,  dried  in  vacuo 
over  oil  of  vitriol,  powdered,  and  subjected  to  the  benzol  process, 
whereby  they  are  separated  into  the  three  different  compounds 
which  have  been  described  under  lecithin.  The  compound  in- 
soluble in  boiling  benzol  is  the  amidomj^elin  dicadmium  chloride 
compound.  When  the  cadmium  precipitates  are  not  thrown 
together,  but  treated  separately  by  the  benzol  process,  it  is 
observed  that  those  obtained  from  the  earliest  spirit  solutions 
contain  only  little  amidomyelin,  while  this  ingredient  gradually 
increases  in  quantit}^  until  in  the  cadmium  precipitate  obtained 
from  the  ninth  or  tenth  solution  there  is  found  as  much  as  40  per 
cent,  of  the  salt  insoluble  in  boiling  benzol. 

Amidormjeliii  Dicadmium  Chloride  Com^joimd,  InsohdtJe  in  Boiling 
Benzol  from  Ox  huitery  after  Lead  Process. 

Sf/nopsis  of  Ancdijses : 

(1.)       (2.)    (3.)      (4.)     (5.)      (6.)      (7.)  (8.) 
C       43-78    43-87    —       —       —       —       —  — 

H        7-68      7-72    _       —       —  — 

N  —        —    2-38     2-55     2-38     —  — 

P  _____      2-57     2-58  — 

Cd  —        ______  17-99 

CI  ________  11-42 

Mean  of  Ancdyses  and  Theory  of  Formvla. 

Percents.  -^At  Wgts.  -^P  =  1.     ^N  =  l.  Theory. 

C      43-825  3-652  43-73  42-  C,,    528  ] 

H       7-70  7-70  92-2  88-  H,.,     92  | 

N        2-43  0-1735  2-07  2-  N.,      28  |^  839 

P        2-59         0-0835  1-  0-96  P"      31  j 

O      14-045  0-8775  10-5  10-  O^o    160  J 

Cd     17-99  0-1606  1-92  1-84  Cd^   224  ( 

CI     11-42  0-321  3-84  3-70  CI,    142  /  ^^"^ 

100-000  1205 


C44H3,N,POio(C(iCl2),  requires  30-37  per  cent.  CdCl,. 

found  29-41 
C44H92N2POioCdCl2    requires  17-90 

Preparation  of  Free  Amidom.yelin  from  the  Cadmium  Chloride 

(a)  By  the  Hydrothion  Process. — The  cadmium  chloride  salt 
described  in  the  foregoing  is  finely  powdered,  suspended  in  spirit, 
and  the  mixture  is  saturated  with  hydrothion  at  the  ordinary 
temperature.  It  is  then  heated  in  a  water-bath  until  the  spirit 
boils,  while  the  introduction  of  the  sulphuretted  gas  is  continued 
until  the  cadmium  is  all  transformed  into  the  yellow  sulphide. 
AVhen  a  filtered  sample  of  the  solution  is  no  longer  altered  by 
hydrothion,  the  whole  is  isolated  by  filtration  on  a  heated  funnel. 
On  cooling  it  crystallises,  the  quicker  the  more  concentrated  it  is. 
After  twenty-four  hours'  standing  the  crystals  are  collected,  washed 
with  spirit  and  pressed,  redissolved  in  a  minimum  of  spirit  (in 
which,  before  dissolving,  they  melt  into  an  oil),  and  again  allowed 
to  crystallise.  This  process  is  repeated  until  crystals  and  mother- 
liquor  are  both  perfectly  colourless.  In  this  process  there  is  the 
danger  that  some  of  the  amidomyelin  is  decomposed  under  the 
influence  of  the  four  molecles  of  hydrochloric  acid  which  are  set 
free  by  the  decomposition  of  the  cadmium  chloride.  This  chemo- 
lysis  may  yield  some  fatty  acid,  which  may  remain  mixed  with  the 
amidomyelin,  and  is  difficult  to  remove.  In  consequence,  the 
carbon  and  hydrogen  of  the  free  body  may  be  found  higher  than 
the  theory  derived  from  the  salt.  The  free  body  also  retains  some 
hydrochloric  acid — in  the  first  instance,  less  than  1  per  cent, 
(found  0*93  per  cent.  CI) — which  diminishes  to  a  trace  by  repeated 
crystallisation  from  spirit.  But  to  remove  this  hydrochloric  acid 
entirely  requires  a  circumstantial  process  and  the  employment  of 
silver  oxide  or  mercuramin,  and,  again,  hydrothion  and  frequent 

(6)  By  Dialysis. — The  cadmium  compound  is  suspended  in 
w^ater,  and  placed  in  a  corrugated  piece  of  vegetable  parchment, 
folded  like  a  plaited  filter,  and  placed  inside  a  funnel.  The 
funnel  is  closed  with  a  cork,  or  some  kind  of  tap,  at  its  lower 
aperture,  and  the  space  between  the  funnel  and  parchment  is 
filled  with  distilled  water.  This  is  renewed  as  long  as  it  contains 
cadmium  chloride,  indicated  by  sulphide  of  ammonium  and  nitrate 


of  silver.  The  amldomyelin  is  at  last  found  to  be  completely  dissolved 
in  the  watei\  and  the  solution  can  be  filtered  clear  through  the 
densest  filtering-paper.  When  this  solution  is  gently  warmed,  it 
sets  into  a  jelly.  This  latter  may  be  evaporated  on  the  water- 
bath,  with  constant  stirring,  to  near  dryness.  The  residue  is 
dissolved  in  hot  spirit,  the  solution  treated  with  hydrothion  to 
remove  a  trace  of  cadmium,  and  allowed  to  cool  and  stand. 
White  amidomyelin  crystallises,  to  be  purified  by  recrystallisation, 
etc.,  as  above  described. 

{(:)  From  the  Acid  Mother-liquors,  filtered  from  the  crystallised 
amidomyelin,  the  hydrochloric  acid  is  removed  by  mercuramin 
added  in  fine  powder,  with  stirring  and  warming.  When  the 
powder  does  not  any  longer  change  colour,  but  retains  its 
canary-yellow  tint,  all  the  acid  is  precipitated.  The  solution  is 
filtered  warm,  and,  yet  warm,  treated  with  a  little  hydrothion  to 
remove  the  trace  of  mercuramin  which  is  dissolved  in  the  hot 
spirit.  It  is  then  concentrated,  and  allowed  to  crystallise  ;  or  if 
coloured,  it  is  mixed  with  cadmium  chloride  solution,  and  the 
washed  cadmium  chloride  compound  is  treated  anew  as  above 

Properties  of  Amidomyelin. 
Amidomyelin  crystallises  in  snowy-white  microscopic  plates  and 
needles,  arranged  in  stars  and  disposed  in  irregular  masses.  They 
dry  in  vacuo  over  oil  of  vitriol  to  a  perfectly  white  mass,  which  is 
easily  powdered,  and  can  be  dried  in  the  water-oven  below  100°. 
With  sugar  and  oil  of  vitriol  amidomyelin  gives  the  purple  of 
Kaspail's  reaction  rather  quickly  and  deeply  ;  it  is  at  present  not 
known  whether  the  reaction  is  due  to  the  presence  of  the  oleyl, 
cholyl,  or  sphingosyl  radicle  in  the  molecle  of  the  amidomyelin. 
The  remarkable  solubihty  of  the  freshly  dialysed  amidomyelin  in 
cold  pure  water,  and  insolubility  in  slightly  warmed  water,  must 
again  be  pointed  out.  The  change  which  it  undergoes  when  its 
watery  solution  is  warmed  is  permanent  :  the  jelly  j^roduced  by 
warmth  does  not  redissolve  on  cooling.  This  phenomenon  is  of 
great  importance  in  the  study  of  the  functions  of  the  immediate 
principles  in  the  brain  ;  it  is  calling  for  further  investigation,  and 
comparison  with  the  bearing  of  the  other  phosphatides  under 
similar  conditions.  One  of  these,  not  yet  accurately  identified, 
has  the  property  of  being  slimy  and  difi'used  and  unfilterable  in 
cold  water,  while  becoming  hard  and  contracted  in  boiling  water. 


so  that  the  water  can  be  filtered  off.  This  substance,  with 
fresh  cold  w^ater,  gradually  resumes  the  slimy  greatly  hydrated 

Theory  of  Amiclomyelin  (Ox)  as  deduced  from  its  Cadmium  Chloride 
Compound,  and  Comparison  with  the  Theory  of  Sphingomyelin 

Taking  the  organic  molecle  from  the  analysed  CdCU  salt,  with 
29-42  per  cent.  CdCl^,  namely  70*59  per  cent.,  and  calculating 
elements  for  100,  we  get — 

„      .    .,        1.  Sphingomyelin  ffives — 

For  Amidomyelin-  4oH,o4N;P09  +  H,0. 


-rAt.  Wts. 


At.  Wts. 





.  5-179 








































Diagnosis  and  Separation  of  Amidomyelin  from  Sphingomyelin. 

Elementary  analysis,  with  special  regard  to  the  relations  be- 
tween N,  P,  and  C,  is  as  yet  the  only  means  of  establishing  a 
diagnosis  between  these  two  principles.  It  is  satisfactory  that  in 
the  first  steps  of  brain  extraction  they  separate  in  the  main ; 
amidomyelin  remains  with  paramyelin  and  lecithin,  while  sphingo- 
myelin remains  with  the  cerebrosides  and  cerebrinacides.  But 
the  analyses  of  sphingomyelin  in  early  stages  of  purification  make 
it  probable  that  it  is  mixed  with  a  mononitrogenised  phosphatide 
as  insoluble  in  cold  spirit  as  itself,  a  body  closely  resembling  or 
identical  with  paramyelin.  From  paramyelin  amidomyelin  is 
easily  separated  by  the  benzol  process  aj^plied  to  cadmium 
chloride  salts.  This  process  will  therefore  aid  to  separate  para- 
myelin from  sphingomyelin  also.  But  it  has  not  yet  been  possible 
to  exactly  fix  the  bearing  of  sphingomyelin  and  its  cadmium 
chloride  salt  towards  benzol,  nor  to  establish  its  absolute  diagnosis 
and  absolute  separation  from  amidomyelin  when  both  occur  in  a 
state  of  admixture  with  each  other.  Neither  has  there  been  time 
or  material  for  the  study  of  the  chemical  constitution  of  amido- 
myelin by  means  of  the  chemolytic  method,  which  I  have  shown 


abundantly  in  the  course  of  these  researches  to  be  the  only  means 
for  obtaining  jirecise  final  knowledge  regarding  the  atomic  com- 
position and  weight  of  these  marvellous  ingredients  of  the  brain, 
nerves,  and  protoplastic  centres. 

2.  Amidokephalin,  its  Isolation,  Analysis  and  Compounds. 

Amidohephalin. — The  following  preparation  was  made  from  a 
specimen  of  crude  kephalin  which  had  not  undergone  the  purifying 
process  w^ith  water,  filtration,  and  hydrochloric  acid.  It  had  been 
thrice  precipitated  from  ether  by  alcohol,  and  when  last  dissolved 
in  ether,  had  stood  during  twenty-four  hours  in  ice,  to  deposit 
traces  of  myelin  and  sphingomyelin. 

Summary  of  Analyses  of  the  Free  Kephalin  emjjloyed  in  this 

-^by  At.  Wgts. 

P  as  1. 

P  =  3. 



























It  will  thus  be  seen  that  all  the  elements  are  in  proportions 
required  by  pure  kephalin,  except  the  nitrogen,  which  is  six-tenths 
of  an  atom  too  high,  or  amounts  to  nearly  five  atoms,  if  three 
atoms  of  phosphorus  are  assumed. 

If,  as  is  probable  from  analogy  v/ith  amido-  and  sphingomyelin, 
there  are  kephalins  containing  amidated  acids,  as  proximate  con- 
jugated compounds,  which  amidated  acids  have  also  now  and 
then  been  found  in  the  chemolyses  of  kephalin,  then  it  might  be 
supposed  that  out  of  six  fatty  acid  radicles  in  three  molecles  of 
kephalin,  two  fatty  acid  radicles  were  amidated. 

The  facts  are  expressed  by  the  formula — 

t'«H,„K,PO„  ) 

The  preparation  was  jjroved  to  be  free  from  sulphur  by  special 
analysis.  Some  anomalies  in  details  evidently  do  not  yield  to 


Transformation  of  this  Freparoiion  into  Lead  Salt. 
The  specimen  of  kephalin  was  therefore  again  frozen  in  ether, 
and  deposited  a  vestige  of  white  matter ;  the  clear  sohition  was 
then  poured  into  absolute  alcohol  containing  lead  acetate  ;  the 
precipitate  was  filtered,  washed,  suspended  in  absolute  alcohol, 
warmed  to  45°  to  50°,  filtered  hot,  to  extract  soluble  matters. 
No  deposit  occurred  in  this  alcohol  on  cooling.  The  lead  salt 
was  dried  in  vacuo,  powdered,  and  found  highly  electric.  It  was 
suspended  in  and  extracted  with  ether. 

Summarij  of  Analyses: 

C  44-U 

H  6-583 

N  1-07 

Pb  27-86  27-49    26-10    26-54  Mean  -  26-99 

P  2-97  3-09                       Mean==  3-03 

0  18-25 


Calculation  shows  that  in  this  compound  the  lead  does  not 
stand  in  any  stoichiometric  relations  to  any  one  element.  It  is  in 
excess  by  about  one-fourth  over  the  quantity  it  should  be  if  one 
atom  of  kephalin  were  combined  with  one  atom  of  lead.  De- 
ducting the  lead,  and  calculating  the  organic  matter,  i.e.  73-01  as 
100,  we  get — 

K  in  Pb  salt.       Free  K  before.   Pure  K  gives.   Theory  requires. 

C  60-5  59-51  60-00  60-28 

H  9-1  9-31  9-39  9-44 

N  1-46  2-73  1-68  1-67 

P  4-06  3-64  4  27  3-70 

0  25-02  24-31  24-66  24-88 

100  00  100-00 
The  ether  and  lead  treatment,  the  combination  and  purification 
thereby  eff'ected,  have  therefore  brought  this  kephalin  much  nearer 
to  the  composition  of  the  purest. 

3;  Sphingomyelin. — Type  of  the  Dmiidated  Phosphatides, 


Chemolysis,  and  Compounds. 
In  chemical  researches  which  have  to  deal  with  the  separation 
of  the  ingredients  of  complex  mixtures,  the  difficulties  generally 
rise  with  the  atomic  weights  of  the  bodies  to  be  treated.  Of 


this  rule,  S2)hingomyelin,  a  body  the  atomic  weight  of  which  is 
probably  one  of  the  highest  after  those  of  the  albuminous  class, 
has  furnished  a  striking  confirmation. 

Sphingomyelin  is  the  principal,  but  not  the  only,  phosphorised 
ingredient  of  the  so-called  cerebrin  mixture,  'which  remains  when 
white  matter  is  exhausted  by  ether.  Out  of  this  mixture  there 
have  been  isolated  entire  series  of  immediate  principles  ;  first  and 
best  studied,  the  cerehrosides,  with  phrenosin  as  their  chief ; 
secondly,  the  cerehrlnacides,  which  contain  more  oxygen  than  the 
former,  and  combine  with  lead ;  thirdly,  bodies  containing  sulphur 
as  an  essential  ingredient,  hence  termed  cerehrosnlphatides.  To 
these  we  have  now  to  add  the  description  oi  peculiar  ijliosphatides, 
and  certain  nitrogenised  substances  free  from  phosphorus,  which 
may  be  termed  nitrogenised  fats  or  amidolipotides.  The  processes 
described  in  the  following  are  those  which  actually  led  to  the 
discovery  by  which  they  were  rewarded.  But  it  is  probable  that, 
after  a  complete  knowledge  of  the  properties  of  the  newly  dis- 
covered bodies  has  been  obtained,  these  processes  may  be  much 
simplified  and  shortened. 

Process  of  separating  apparently  homogeneous  Crystallised  Bodies  from 
the  Alcohol  used  for  the  separation  of  the  Cerebrosides ;  which 
Bodies  will  he  shown  to  he  Mixtures  hy  Reagents. 

After  the  removal  of  phrenosin  and  kerasin  by  crystallisation 
from  absolute  alcohol  frequently  repeated,  there  remained  alco- 
holic solutions,  which  made  no  further  deposit  on  standing.  These 
were  distilled  to  a  small  bulk,  and  deposited  a  white  crystallised 
matter.  (An  attempt  to  separate  anything  out  of  the  matter  by 
benzol  proved  abortive ;  cold  benzol  extracted  but  little,  on 
application  of  heat  all  dissolved,  and  on  cooling  the  mixture  set 
into  an  unmanageable  jelly.  The  benzol  was  therefore  distilled 
off,  and  the  matter  treated  anew  with  spirit.)  The  crystalline 
matter  was  dissolved  in  hot  spirit  of  85  per  cent,  strength,  and 
an  alcoholic  solution  of  lead  acetate  was  added,  after  this  a  slight 
excess  of  ammonia.  The  cerebrinacides  contained  in  the  body 
were  thus  precipitated  as  lead  salts.  From  these  the  solution 
was  separated  hot  by  filtration.  After  cooling,  the  alkaline 
mother-liquor  was  separated  from  the  crystalline  deposit.  The 
washed  crystalline  mass  was  dissolved  in  hot  spirit,  and  left 
much  matter  in  a  fused  state  (second  lead  stearoconote).    A  part 


of  the  matter  being  yet  insoluble  lead  compound  should  remain 
undissolved  ;  but  when  fused  it  encloses  a  quantity  of  soluble 
matter,  which  then  remains  inaccessible  to  the  spirit.  It  has 
been  found  usefid  to  emulge  the  crystalline  matter  with  some 
water  before  heating  it  with  spirit.  This  resolution  in  hot  spirit 
and  recrystallisation  are  repeated  four  times,  or  until  no  lead  salt 
remains  insoluble,  and  until  the  product  is  uniformly  white,  and 
crystallised  in  stars  and  rosettes  of  needles,  clearly  visible  under 
the  microscope.    It  is  dried  in  vacuo. 

Properties  of  the  Product.— With  water  it  forms  a  permanent 
jelly  or  paste  like  starch  pap.  With  sugar  and  sulphuric  acid  it 
gives  an  immediate  purple  reaction  ;  with  sulphuric  acid  alone  it 
becomes  thoroughly  purple.  Heated  to  between  90°  and  100°  in  a 
water-oven,  it  becomes  a  little  soft  and  a  little  coloured  ;  when 
cold,  it  becomes  again  pulverisable.  It  fuses  at  about  150°, 
assuming  a  brown  colour.  It  yields  to  absolute  ether-alcohol  a 
considerable  amount  of  matter,  which  crystallises  in  the  original 
rosettes  and  clichotomically  branched  masses,  like  lycopodium. 

Preliminarij  Quantations  of  Elements. — Synopsis  of  Results. 


in  100. 

-^At.  Wgt. 

-^P  =  l. 






11  55 















These  data  show  that  the  body,  though  crystallised  as  described, 
was  yet  a  mixture.  Its  principal  ingredients  were  sphingomyelin, 
in  which  P  :  N  =  1  :  2,  and  Jcerasin,  which  latter  mainly  explains 
the  excess  of  carbon  and  nitrogen  and  attached  water,  as  will  be 
shown  below. 

Comparison  with  this  Rosette  or  LycopocUum-Uke  Body  of  a  similar 
Body  obtained  from  the  Cerebrin  Mixture  by  Ether,  together  lulth 
the  Kephalin,  etc. 

The  ether  extracts  from  white  matter  containing  all  kephalin, 
myelin,  cholesterin,  etc.,  were  concentrated  and  mixed  with  an 
alcoholic  solution  of  lead  acetate.  Kephalin  and  myelin  became 
insoluble  as  lead  salts.  When  the  precipitated  matters  were 
boiled  with  spirit,^nd  the  filtrate  wa?.  allowed  to  cool,  cholesterin, 
together  with  a  lead  compound  and  the  new  body  were  deposited. 


The  deposit  was  isolated,  dried,  and  extracted  with  ether  not  in 
excess.  Cholesterin  dissolved,  while  the  lead  salt  and  new  body 
remained  undissolved.  The  latter  mixture  was  treated  with 
boiling  alcohol,  which  dissolved  the  new  body,  and  deposited  it 
on  cooling  in  crystalline  rosettes,  while  the  lead  salt  remained 
undissolved  as  a  fused  mass.  By  frequent  recrystallisation  of 
the  new  body  as  long  as  it  left  any  fused  lead-compound,  it  was 
at  last  obtained  quite  free  from  lead  and  white. 

Chemical  and  Physical  Frojjerfies. — White  crystalline  mass. 
Becomes  soft  at  90°,  without  loss  of  water.  Gives  Kaspail's 
reaction  with  and  without  sugar,  from  which  the  presence  of  a 
cerebroside  may  be  inferred.  The  lead  compound  gave  the  Easpail 
reaction  with  and  without  sugar,  if  at  all,  very  indistinctly. 

Analyses  of  the  second  Rosette  Body. — Synopsis  of  Results. 


-^At.  Wgt. 

^P  =  l. 





















The  crystallised  body  just  analysed  is  a  mixture  of  a  dinitro- 
genised  phosphatide,  sphingomyelin,  with  a  cerebroside,  as  was 
clearly  shown  by  the  application  of  reagents.  But  the  nature  of 
the  cerebroside  in  this  case  was  not  ascertained  as  in  the  former 

Isolation  of  Spjliiagcnnyelin  by  Cadmium  Chloride  Process. — Many 
attempts  (of  which  only  two  have  been  described  in  the  fore- 
going) having  been  made  to  isolate  a  constant  product  by  mere 
crj^stallisation  with  solvents,  without  success,  the  cadmium  chloride 
process  was  again  adopted.  The  reagent  was  mainly  applied  to 
cold  alcoholic  solutions,  and  had  the  following  effect.  A  pre- 
cij^itate  of  CdCl^  salt  ensued  immediately.  If  this  was  filtered 
off  quickly,  a  second  more  gelatinous  precipitate  fell,  consisting  of 
almost  pure  kerasin.  The  CdCl^  salt  also  contained  yet  some 
kerasin.  From  this  it  was  separated  by  boiling  spirit ;  the  CdCl^ 
salt  was  deposited  mainly  above  28°,  the  kerasin  entirely  below 
28°,  and  on  long  standing  provided  that  the  amount  of  kerasin 
did  not  rise  above  1  part  in  321  parts  of  spirit.  Of  the  CdCL 
salt,  spirit  retains  less  than  a  half  per  cent,  (weight  in  volume)  in 
solution.    It  is  probable  that  the  body  or  bodies  which  combine 


with  CdCl^  (sphingomyelin  and  other  phosphatides)  on  the  one 
hand,  and  kerasin  on  the  other  hand,  keep  each  other  in  solution 
by  some  attraction  which  they  have  for  each  other,  in  which 
sphingomyelin  acts  as  base,  kerasin  as  acid,  the  result  being  a 
kind  of  salt  which  is  more  soluble  in  spirit  than  each  of  its  com- 
ponents by  itself.  The  alcoholic  solution  from  which  the  CdCl^ 
salt  and  kerasin  have  been  precipitated,  must  be  allowed  to  stand 
long,  and  be  repeatedly  concentrated,  to  remove  all  kerasin.  It 
then  yields  a  precipitate  with  platinum  chloride  and  hydrochloric 
acid,  which  is  a  compound  of  a  phosphorised  and  nitrogenised 
body,  assurin,  with  the  reagents  employed.  The  mother-liquor 
yields  Icrinosin  and  hregenin,  nitrogenised  matters  free  from  phos- 
phorus, and  belonging  to  the  new  class  of  amidated  lipotides  or 
nitrogenised  fats,  as  will  be  fully  described  lower  down. 

Gradual  Purification  of  the  CdCl.2  Salt  of  SjMngomijelin  by  recrystaU 
lisation  from  boiling  Spirit  and  Extraction  with  boiling  Ether. 

In  the  course  of  these  processes  it  was  found  that  the  pre- 
cipitates might  contain  varying  quantities  of  CdCl2,  and  that 
these  niight  correspond  to  several  compounds.  Sphingomyelin 
might  combine  vrith  one  or  two  molecles  of  CdCl^ ;  the  second 
phosphatide  might  combine  with  one  molecle  of  CdCl^  only,  being 
a  mononitrogenised  body,  probably  paramyelin.  The  CdCl2  might 
also  be  depressed  by  the  admixture  of  kerasin.  It  was  also  found 
that  the  CdCl.,  would  shift,  so  as  to  increase  in  one  fraction,  while 
diminishing  in  another  of  a  previously  unitary  preparation. 

The  changes  of  these  salts  in  general,  and  the  extraction  of  the 
kerasins  and  other  admixtures  in  particular,  were  followed  analy- 
tically. Thus  a  CdCl  salt  gave  5-97  per  cent.  CI  and  10-89  per 
cent.  Cd=  16-86  per  cent.  CdCl^.  The  5-97  per  cent.  CI  require  in 
theory  9*41  per  cent.  Cd  =  15-38  per  cent.  CdCl^.  The  salt  here 
obtained  was  the  one  with  one  molecle  of  CdCl^ ;  sphingomyelin 
with  51  carbon  atoms  and  CdCl2  postulates  164  per  cent.  CdCU  ; 
the  body  with  53  carbon  atoms  requires  15-98  per  cent.  CdCl2. 

Another  salt  from  ox  cerebrosides  mother-liquor  of  recrystallisa- 
tion  was  a  mixture  of  sphingomyelin  CdCl^  in  which  N  :  P  =  2  :  1, 
and  of  a  phosphatide  CdCl2  salt,  in  which  N  :  P  =  1  :  1,  probably 
paramyelin.  The  salts  were  crystallised  from  hot  spirit  above 
30°,  and  recrystallised  until  free  from  kerasin. 

They  contained  13-14  per  cent.  Cd,  3*24  per  cent.  P,  and 


9-12  per  cent.  CI,  2-28  per  cent.  N,  50-70  per  cent.  C,  and  9-08 
per  cent.  H. 

The  chlorine  found  in  analysis  (1)  postulates  14* 3  per  cent.  Cd. 
There  is,  therefore,  a  slight  deficiency  of  this  element.  The 
organic  molecle  has  therefore  to  be  calculated  by  deducting  the 
latter  larger  figure  for  Cd,  namely,  14 '3  per  cent.,  thus  : 

CdCl^    -       -       -    23-42  per  cent. 
Organic  molecle     -    76*58  „ 


This  quantity  of  CdCl^  indicates  that  the  mixture  contains 
sphingomyelin  monocadmium  chloride  with  sphingomyelin  di- 
cadmium  chloride,  bodies  which  will  be  discussed  more  explicitly 
lower  down.  The  nitrogen  is  to  the  cadmium  chloride  in  such  a 
proportion  that  the  basicity  of  sphingomyelin  is  unsatisfied  to 
the  extent  of  about  one  quarter,  or  upon  two  atoms  of  nitrogen 
there  is  very  nearly  one  and  a  half  molecle  of  cadmium  chloride 

Synopsis  of  the  foregoing  Analytical  Results. 

Per  cents.  -^-At.  Wgts. 

2-  28  0-162 

3-  24  0-104 

I  23-42 





Calculation  of  Elements  in  100  of  Organic  Molecle. 


H-At.  Wgts. 





















The  relations  of  C :  X  are  the  same  as  those  of  the  same  elements 
in  the  crystallised  free  body,  which  will  be  described  further  on. 
Consequently  the  phosi)horus  is  somewhat  too  high. 


Further  Purification  of  the  Conipound  bj  Ether,  and  by  recrydallisa- 
tion. — The  mixture  was  now  subjected  to  a  process  of  purification 
by  being  exhausted  in  a  closed  apparatus  with  boiling  ether. 
AVhen  new  ether  failed  to  extract  anything  during  ah  entire  day 
of  boiling,  the  compounds  were  recrystallised  from  spirit,  again 
dried,  and  again  exhausted  with  ether.  If  now  fresh  ether  ex- 
tracted nothing,  the  salts  were  considered  to  be  fully  exhausted. 
(Some  krinosin  and  bregenin  were  extracted.)  In  this  manner  a 
number  of  prej)arations  were  purified,  with  the  result  that  in  all 
the  carbon  sank  a  little,  while  cadmium  chloride  rose  in  quantity, 
but  nitrogen  remained  to  phosphorus  as  2  :  1*28,  as  will  be  seen 
from  the  following  analyses. 

Synojms  of  Quantations  and  Theory  of  Salt. 

Percents.  -j-At.  Wgts. 

C      46-11  3-84 

H       8-66  8-66 

N       2-24  0-160 

P       3-22  0-104 
0  14-37 

Elements  and  Theory  of  Organic  Matter. 

Percents.  -^At.  Wgts.  -^N  =  2 

C    61-80  5-15  48-5 

H   11-60  11-60 

N     3-00  0-214  .  2- 

P     4-31  0139  1-28 

0    19-29  1-205 

We  have  therefore  here  also  the  phosphorus  too  high  for  sphin- 
gomyelin, namely,  N  :  P  =  3  :  2,  from  which  it  may  be  surmised 
that  the  admixture  was  partially  a  mononitrogenised  phosphatide 
(paramyelin  ?),  partly  a  diphosphatide  such  as  will  be  described 
further  on. 

As  no  even  relation  between  nitrogen  and  phosphorus  could  be 
obtained  by  any  kind  of  treatment,  particularly  frequent  recrys- 
tallisation,  to  which  the  compound  was  subjected,  it  was  deemed 
necessary  to  decompose  it  and  study  the  free  body.  It  was 
evident  from  the  relation  C:N  =  51-8:2  that  the  organic  body 
was  not  a  phosphatide  of  the  lecithin  group,  in  which  C  :N  =  42 : 1, 


or  thereabouts,  while  the  amount  of  nitrogen  pointed  to  the  pro- 
babihty  that  the  body  was  constituted  simihirly  to  the  amido- 
myelins  which  had  been  hypothetically  assumed  to  exist  in 
analysed  CdCl.,  and  PtCl^  compounds.  In  fact,  it  was  at  once 
perceived  to  present  the  proportions  between  C  and  N  which  had 
been  observed  upon  apomyelin  described  in  my  first  research  on  the 
brain.  But  as  it  had  been  left  doubtful  whether  this  apomyelin 
was  not  a  product  rather  than  an  educt,  great  care  was  taken 
to  prevent  any  chemolytic  influence  from  acting  on  the  body,  so 
that  the  doubt  just  mentioned  might  be  eliminated.  The  crys- 
tallisation of  the  free  substance  showed  at  once  the  presence  of 
fico  imnciplcs,  of  which  the  first,  sphingomyelin,  was  obtained  pure 
by  crystallisation,  while  the  second  one  was  obtained  pure  by 
more  circumstantial  processes  to  be  described  later. 

PrepardtioR  of  pure  Sphingoniijeliii  from  its  Cadmium  Chloride 

Removal  of  the  Cadmium  by  Diffusion  and  Dialysis. — AYhen  the 
compound  is  placed  in  Avater,  this  will  extract  much  of  the  CdCl.,, 
but  not  all,  by  dissociation  and  diffusion.  But  the  liberated 
sphingomyelin  is  in  the  state  of  colloidation,  which  increases  with 
the  length  of  contact  with  water  until  it  reaches  its  maximum. 
The  liquid  can  thus  no  longer  be  filtered  from  the  sphingomyelin, 
as  the  latter  immediately  obstructs  the  pores  of  the  filter. 

Dialysis  may  be  resorted  to,  the  apparatus  being  arranged  with 
plaited  vegetable  parchment  dialysers  as  described  on  p.  101. 
AVhen  the  dialysate  is  free  from  CdCl^,  the  sphingomyelin  and 
water  paste  must  be  concentrated,  dissolved  in  hot  spirit,  treated 
with  hydrothion  to  remove  the  last  portions  of  cadmium,  and 
set  to  crystallise. 

The  sphingomyelin  which  was  examined  in  the  first  four 
analyses  to  be  related  below  was  prepared  with  the  aid  of 
dialysis,  as  follows  :  40  g.  CdCl.,  salt  was  boiled  with  1  litre  spirit ; 
23  g.  dissolved,  while  13  g.  remained  insoluble  in  the  quantity  of 
spirit  mentioned.  The  hot  spirit  solution  deposited  a  quantity 
of  salt  above  30^  and  was  filtered  at  30°.  The  salt  thus  obtained 
was  subjected  to  dialysis,  and  washed  with  water  until  free 
from  chlorine.  It  was  then  recrystallised  from  spirit,  and  dried 
at  100". 

The  liquid  which  had  deposited  the  CdCU  salt  above  30°  was 


evaporated,  and  the  deposit  filtered  off.  It  was  also  decomposed 
with  water,  and  the  body  free  from  CdCl2  was  analysed.  It 
yielded  results  which  have  been  recorded  separately.  If  my 
object  were  solely  that  of  a  mere  chemist  in  search  of  new  pure 
compounds,  I  should  have  thrown  this  and  other  mother-liquors 
away.  But  the  object  of  physiological  and  pathological  research  is 
not  to  find  some  principles  which  will  pay  the  chemical  operator, 
but  to  find  all  the  principles  which  may  be  contained  in  an  organic 
physiological  or  pathological  mixture. 

The  following  process  yields  sphingomyelin  in  a  shorter  time 
than  dialysis.  The  purified  salt,  free  from  kerasin  and  all  matters 
which  ether  can  extract,  is  susj)ended  in  spirit,  and  treated  with 
hvdrothion  to  saturation.  The  fiask  containinsr  the  mixture  is 
now  placed  in  a  water-bath,  the  water  of  which  is  gradually 
raised  in  temperature  until  the  spirit  in  the  flask  boils.  The  in- 
fluence of  the  sulphuretted  gas  is  continued  until  a  filtered  sample 
of  the  spirit  solution  is  not  changed  by  the  hydrothion  any  more. 
The  mixture  is  now  filtered  through  paper  in  a  funnel  kept  hot 
by  a  steam-jacket.  The  filtrate  is  left  to  crystallise.  It  yields 
sphingomyelin,  etc.,  partly  as  hydrochlorate,  which  are  collected 
on  a  filter,  washed  with  spirit,  pressed  between  bibulous  paper, 
and  dried  in  vacuo  over  oil  of  vitriol.  The  neutral  and  dry  salts 
are  now  again  dissolved  in  warm  spirit,  and  to  the  solution  is 
added  gradually,  and  in  small  quantities,  as  much  finely  pul- 
verised mercuramin  as  may  be  necessary  to  bind  and  retain  in  the 
precipitate  all  the  hydrochloric  acid  combined  with  the  phos- 
phatides. When  an  excess  of  mercuramin  is  present — i.e.^  when 
the  deep  canary-yellow  colour  of  the  mercuramin  is  no  longer 
changed  to  white,  but  remains  as  a  yellow  deposit  at  the  bottom 
of  the  flask,  distinct  from  the  white  mercuramin  hydrochlorate — 
then  the  organic  principles  are  free  from  hydrochloric  acid ;  the 
filtered  solution,  on  cooling,  deposits  first  sphingomyelin,  to  be 
purified  by  recrystallisation ;  the  concentrated  mother-liquor  de- 
posits the  mononitrogenised  companion  mainly.  (Without  the 
mercuramin  treatment  the  sphingom/elin  may  retain  from  0  8  to 
1-32  per  cent.  HCl.) 

Physical  and  Chemical  Properties  of  Sphingomyelin. — Sphingo- 
myelin is  easily  soluble  in  hot  spirit  or  absolute  alcohol,  and 
crystallises  therefrom  in  dense  white  masses,  needles,  stars,  and 
hexagonal  j)lates.    It  does  not  become  waxy  after  drying,  but 



retains  a  pulverulent  dryness.  It  is  little  soluble  in  cold  absolute 
alcohol,  but  can  be  separated  thereby  from  phrenosin,  which  is 
less  soluble,  and  from  lecithin,  which  is  more  soluble.  It  is 
almost  insoluble  in  ether,  even  when  some  hydrochloric  acid  has 
been  added.  It  cannot  be  separated  from  kerasin,  to  which  it 
stands  in  the  relation  of  a  base,  by  recrystallisation  alone.  The 
intervention  of  cadmium  chloride  is  necessary  to  effect  this 
sej^aration.  The  compound  of  sphingomyelin  with  cadmium 
chloride  is  less  soluble  in  spirit  than  the  pure  sphingomyelin,  and 
is  deposited  in  a  much  shorter  time  and  at  higher  temperatures 
than  kerasin ;  for  the  sphingomyelin  CdCl2  falls  above  28°, 
kerasin  (in  solutions  which  contain  less  than  1  g.  in  321  cc.  of 
spirit  of  84  per  cent.)  below  28°,  on  standing.  Sphingomyelin 
swells  in  water,  and  becomes  distributed  in  it  so  as  to  form  a 
turbid  semisolution  or  emulsion.  In  the  course  of  dialysis  it 
sometimes  contracts  and  sinks  in  the  w^ater.  Its  compounds, 
particularly  those  with  CdClg,  become  decomposed  under  the  in- 
fluence of  water ;  sphingomyelin  assumes  the  colloid  form,  and 
the  combined  metals  or  salts  pass  into  solution  in  the  water.  On 
this  property  rests  the  process  for  liberating  sphingomyelin  from 
crystalloids  by  dialysis. 

Quantaiions  of  Elements  in  Sphingomyelin  from  Ox  Brain. 
Synopsis  of  Analyses  and  Theory, 


-hAt.  Wgts. 











9 . 









The  probable  formula  is  C^^H^q^NoPOc)  +  H^O. 

Comparison  of  Sphingomyelin  witli  Aponiyelin  from  Human 

In  'Eeports,'  No.  III.  (1874),  p.  164, 1  have  given  the  analysis  of 
a  specimen  of  a  kind  of  myelin  from  the  human  brain  which  I 
termed  Aponiyelin,  and  which  had  been  obtained  from  a  platinic 
chloride  compound  by  recrystallisation  from  boiling  alcohol,  and 
decomposition  of  the  product  by  hydrothion.  The  following 
figures  were  given  : 


A])omyeliii,  Man. 


—At.  Wgts. 

-f-P  = 























This  was,  therefore,  clearly  a  sphingomyelin  with  54  C ;  like 
the  sphingomyelin  from  the  CdCl^  compound,  it  retained  a  small 
quantity  of  hydrochloric  acid,  which  was  estimated  in  the  analyses 
and  recorded  as  CL  A  sphingomyelin  prepared  from  CdCl^  salt 
by  H2S,  was  found  to  retain  1-32  per  cent.  HCl,  which  is  only 
about  a  third  of  the  theoretical  amount  required  by  a  simple 
hydrochlorate.  In  both  cases  the  hydrochlorate  was  probably 
decomposed  by  the  influence  of  watery  solvents. 

Chemolyses  of  Siohingomyelm,  ivith  a  view  of  ascertaining  its 
Chemical  Constitution. 

I  have  made  four  distinct  experiments  on  this  subject ;  bat  as 
they  are  not  completed,  I  am  only  able  to  state  the  salient  results 
of  the  operations  as  far  as  they  go. 

Experiment  I.  —  Six  g.  sphingomyelin  were  mixed  with  1 2  g. 
barita  hydrate  and  heated  to  105°  during  five  hours.  There  were 
obtained  a  little  sjjhingosin  (precipitated  from  the  alcoholic  extract 
by  sulphuric  acid,  soluble  in  excess),  an  acid  which  differed  from 
sphingomyelin  by  the  absence  of  the  group  of  neurin,  sphingomyelic 
acid,  probably  (if  the  sphingomyelin  employed  had  the  formula 
^53^106-^2-^012)  li^ving  the  composition  C4gHc)5NPOj2-  In  this 
acid,  it  will  be  observed,  P:N=1:1.  There  was  further  ob- 
tained a  barium  salt  soluble  in  ether,  and  an  alcohol  sphingol,  the 
two  latter  bodies  being  products  of  the  continued  decomposition 
of  a  portion  of  sphingomyelic  acid. 

Experiment  II. — Twelve  g.  sphingomyelin,  12  g.  barita  and  50  g. 
water  were  heated  to  100°  for  ten  hours.  There  were  obtained 
1  -1  g.  of  neurin  as  platinic  chloride  salt,  while  theory  requires 
1*3  g.  from  12  g.  sphingomyelin.  No  trace  of  glycerophosplioric  acid 
was  observed.  There  was  a  barium  salt  insoluble  in  alcohol  and 
ether,  which  contained  P:N  =  1:1-02  (P-2-75  per  cent.; 
N='l-27  per  cent.)  sphingomy elate  of  barium.    No  sphingosin 


was  obtained.  But  the  new  alcohol,  sphingoid  was  isolated  in  suffi- 
cient quantit}^  to  be  analysed. 

Anahjsis  of  Sphingoid  a  new  Alcohol,  from  Sphingoniyelin  hj 
Chemolysis  tuith  Barita. 

Dried  at  98°  in  a  platinum  boat. 

Synopsis  of  Analyses  and  Theory. 

Percents.  -^-At  Wgts.  -i-byO  =  l. 

(1)  C     76-30  6-37  9-07 
H     12-78  12-78  18  7 
0     10-92  0-68  1- 

(2)  C  76-34  6-361  9-08 
H  12-45  12-45  17  92 
0     11-21  0-7  1- 

The  new  alcohol  has  therefore  the  composition  expressed  by 
either  CgHjgO,  or  by  C^gHggO^.  In  the  latter  case  it  would  be  the 
third  stearic  isomer. 

Analysis  of  the  Neurin-Platinum-Chloride  Hydrochlorate  ohtdined 
from  this  Chemolysis. 

The  salt  CioH26N,02,  2HCl,PtCl^,  of  atomic  weight  618-4, 

Requires  in  100.  Found  in  Salt. 

Pt  31-921  31-79 
CI    34-44  34-64 

Experiment  HI. — Twenty  g.  sphingomyelin  and  40  g.  barita,  with 
500  g.  of  water,  were  heated  to  135°  during  twelve  hours.  There 
were  obtained  neurin ;  further  a  second  alkaloid  precipitated  by 
sulphuric  acid  from  its  solution  in  absolute  alcohol,  yielding  as 
sulphate  by  analysis  the  formula  2(C2oH4jN02)H2SO^,  being 
possibly  somewhat  impure  sphingosin  ;  sphingol ;  a  fatty  acid, 
which  as  barium  salt  and  as  lead  salt  was  insoluble  in  alcohol  and 
in  ether,  in  the  free  state  had  the  composition  expressed  by  the 
formula  C^gH^^O^,  crystallised,  and  fused  at  57°,  therefore  almost 
as  much  below  ordinary  stearic  acid,  which  fuses  at  69-5°,  as 
neurostearic  acid  fuses  above  this,  namely,  at  84°.  The  acid  is 
therefore  the  fourth  isomer  of  stearic  acid,  the  third  discovered 
in  these  researches,  and  is  named  sphingostearic  acid. 

No  glycerophosphoric  acid  was  ol)tained,  but  the  insoluble 
barium  salt  contained  much  harium  plioxphate^  which  was  isolated 


the  phosphoric  acid  was  combined  with  molybdate  of  ammonium, 
and  fully  identified. 

Experiment  IV. — Twenty-five  g.  sphingomyelin,  50  g.  haiita, 
and  some  water  were  heated  in  the  autoclave  to  105°— 120°  for 
seventeen  hours.  There  were  again  obtained  neurin,  sphingosin, 
sphingol,  barium  salt  insoluble  in  ether,  and  a  neutral  body  mixed 
with  sj)hingol ;  this  latter  mixture  or  compound  had  the  formula 
Cg^HgiNO^,  with  2-18  K 

Some  intermediate,  in  quantity  subordinate,  products,  such  as 
a  barium  salt  soluble  in  ether  and  precipitable  by  alcohol,  remain 
for  further  study. 

Theoretical  Results  of  these  Chemolyses. 

The  conclusions  to  be  derived  from  these  chemolyses  bearing 
upon  the  chemical  constitution  of  sphingomyelin  are  of  the  utmost 
interest  and  importance. 

In  the  first  place,  no  glycerophosphoric  acid  was  obtained 
in  any  one  of  the  chemolyses.  If  I  recall  the  many  experiments 
•made  regarding  the  constitution  of  other  phosphatides,  such  as  of 
kephalin  or  of  lecithin,  and  the  relative  facility  with  which  gly- 
cerophosphoric acid  was  isolated  as  barium  salt  and  identified  as 
calcium  salt,  I  cannot  suppose  for  a  moment  that  glycerophospho- 
ric acid  has  been  present  and  escaped  observation.  I  therefore 
came  to  the  conclusion  that  the  glycerol  found  in  a  portion  of  the 
phosphatides  was  not,  as  has  been  hitherto  supposed,  essential  to 
the  composition  of  those  bodies.  From  this  moment  it  was  also 
evident  that  glycerol  could  not,  or  need  .not,  be  the  basal  radicle 
of  these  compounds,  not  even  of  those  which  contained  it,  and 
that  therefore  the  phosphorised  brain  educts  could  no  longer  be 
considered  as  glycerides,  or  ethers  of  the  alcohol  glycerol,  but  had 
to  be  differently  interpreted.  The  only  feature  common  and 
essential  to  all  the  phosphorised  educts,  and  the  one  from  which 
in  consequence  they  derived  their  appellation,  was  that  they  con- 
tained phosphorus,  which  by  ordinary  analytical  processes  re- 
mained in  the  form  of  phosphoric  acid.  There  was  no  reason  to 
suppose  that  the  phosphorus  was  present  in  the  organic  principles 
in  any  other  form  than  that  of  phosphoryl,  the  radicle  of  phos- 
phoric acid.  (When  they  were  chemolysed  they  took  up  water, 
and  yielded  hydrated  radicles,  such  as  have  been  described, 
acids,  alkaloids,  or  organic  bases,  and  alcohols.)    Consequently  I 


assumed  that  the  ha  sal  radicle  of  all  phosphatides  was  that  of  phosphoric 
acid  ;  that  in  this  acid  one,  two,  or  three  molecles  of  hydrox)jl  might  be 
replaced  hj  radicles  of  alcohols,  acids,  or,  and  that  to  a  moled e 
formed  by  three  such  substittdions  there  might  yet  be  attached,  by  substi- 
tntion  of  an  element  in  a  radicle,  itself  already  substituted  (side -chain) 
m-  by  addition  as  anhyd.ride,  a  fourth  radicle,  and  that  therefore 
sphingomyelin  might  be  constituted  according  to  the  following 
formulae  : 


Phosphoric  acid  =  OP  J  HO 
I  HO 

f  Acid  radicle. 
I  Alcohol  radicle. 
Sphingomyelin  =  OP -{  Base  radicle  (substituted). 

I  Base  radicle  (attached  as  side- chain  or 
[     added  as  anhydride). 

I  repeat  the  formula,  substituting  elementary  formulae  for  the 
functional  symbols  : 

fC.sH^A  1 
[  C,H,,N  J 

To  this  formula  we  are  obliged,  by  the  results  of  the  analyses 
of  the  three  sphingomyelins,  to  add  at  least  2H^0,  perhaps  3H^0, 
and  by  this  operation  we  obtain  a  total  formula  of  C^gHjoiNoPOj^,. 

But  this  last  formula  is  only  a  case  out  of  many  possible 
formulae.  It  is  clear  that  if  the  molecular  formula  of  sphingol 
were  only  C.^H^gO,  the  formula  above  given  would  either  have  to 
be  lowered  to  C^,^,  etc.,  or  the  sphingol  would  have  to  be  assumed 
to  be  doubly  rej^resented.  Neither  hypothesis  enjoys  the  advant- 
age of  probability.  I  therefore  do  not  presume  to  fix  the  exact 
formula  of  sphingomyelin,  particularly  as  I  have  shown  that  there 
are  various  sphingomyelins  (one  being  apomyelin),  but  I  maintain 
that  this  research  has  established  as  a  type  of  brain-educts  sphin- 
gomyelin, which  is  a  phosphatide,  and  contains  an  alcohol  not 
being  glycerol,  an  acid,  and  two  nitrogenised  radi'jles  as  proximate 

Coinpounds  of  Sphingomyelin. — The  body  combines  with  hydro- 
chloric acid,  and  this  compound  is  more  soluble  in  spirit  than  the 
free  body.  The  hydrochlorate  is  easily  decomposed  by  watery 
solvents,  so  that  while  a  monohydrochlorate  should  contain  3 '76 


per  cent.  HCI,  there  were  found  in  a  hydrochlorate  recrystallised 
from  spirit  ow\y  1  -32  per  cent.  HCI. 

Compounds  of  Sphingomyelin  ivitli  Caclmium  Chloride. — The  vary- 
ing quantities  of  cadmium  chloride  in  such  compounds  have  been 
a  source  of  great  trouble  and  doubt,  which  could  only  be  solved 
by  countless  preparations  and  analyses  piloted  by  hypotheses 
and  the  atomic  theory.  Thus  a  salt  was  found  to  contain 
16-86  per  cent.  CdCl^,  and  to  correspond  to  the  formula 
CjjHggN^POiQCdClg,  which  requires  164  per  cent.  CdCl^. 

Another  salt  from  the  human  brain  contained  26-59  per  cent. 
CdClg,  and  was  therefore  supposed  to  be  a  not  quite  saturated 
compound  approaching  that  with  two  molecles  of  CdClg.  For  the 
Q.^-^  sphingomyelin  v;ith  2CdCl2  requires  28  per  cent.  CdCl^ ;  the 
formula  with  C^^  requires  2 7 '9  per  cent.  CdCl^. 

Sphingomyelin  is  therefore,  like  amidomyelin,  a  dipolar  alkaloid, 
and  capable  of  fixing  one  molecle  of  CdCl^  to  each  of  its  two 
nitrogen  radicles. 

Consequently  any  sphingomyelin  and  CdCl^  compound  which 
contains  quantities  of  CdCl2  intermediate  between  16-4  per  cent, 
and  28  per  cent,  is  a  mixture  of  the  monocadmium  chloride,  with 
the  dicadmium  chloride  compound.  Such  a  compound  must  of 
course  contain  P  :  N  =  l  :  2.  Where  these  relations  do  not  subsist, 
but  where  the  relations  of  P  :  N  approach  more  or  less  those  of 
2  :  3,  the  cadmium  chloride  may  be  diminished  by  the  presence  of 
a  compound  with  it  of  a  phosphatide  such  as  paramyelin,  in  which 
P  :  N  =  1  :  1.  It  will  therefore  be  seen  that  the  higher  the  amount 
of  CdCl.2  found  in  a  new  precipitate,  the  more  likely  is  the  body 
to  contain  sphingomyelin  (or  amidomyelin).  If  the  CdCl^  sinks 
much  towards  20  per  cent,  or  below,  the  precipitate  or  crystallisa- 
tion either  contains  much  of  the  monocadmium  chloride  compound, 
or  contains  a  mononitrogenised  body,  which  maybe  either  a  body 
analogous  to  sphingomyelin,  but  containing  one  nitrogenised 
radicle  only,  or  a  lower  phosphatide  such  as  lecithin  or  paramyelin. 

We  have  therefore,  with  regard  to  sphingomyelin,  the  possibility 
of  the  existence  of  two  compounds  and  an  indefinite  number  of 
their  mixtures  in  diff'erent  proportions 

C5.H99N,POio-FCdCl,,  At.  W.  =  1113,  contains  16-4  per  cent. 

C5iH99N2POio-f  2(CdCl2),  At  W.-.1296,  contains  28  per  cent. 


If  there  are,  as  is  probable,  many  sphingomyelins,  then  each 
variety  would  have  its  several  CdCl.,  compounds. 

All  these  CdCl2  salts  are  beautifully  crystallised  and  white. 
When  they  are  recrj^stallised  from  spirit  they  lose  solubility  as 
the  extraction  proceeds.  These  changes  are  particularly  observed 
upon  salts  which  are  not  fully  saturated  with  CdCl.,  :  the  fully 
saturated  salts  behave  in  a  regular  and  stable'  manner.  It  is 
therefore  necessary  in  the  first  crystallisation  to  offer  to  sphin- 
gomyelin an  excess  of  cadmium  chloride,  and  to  test  the  mother- 
liquors  of  recrystaUisation  from  time  to  time  to  see  that  they  do 
not  contain  unsaturated  more  soluble  salt  or  free  sphingomyelin 
in  solution.  Spirit  of  85  per  cent,  strength,  after  having  been 
saturated  boiling  with  the  dicadmium  chloride  salt  and  allowed 
to  deposit  all  it  can  during  twenty-four  hours,  will  keep  in  solu- 
tion half  a  gramme  of  the  salt  in  100  cubic  centimetres. 

N  :  P  =  2  :  2. 


This  body  is  found  in  the  alcohol  extracts  of  the  cerebrin 
mixtures  after  sphingomyelin  and  kerasin  have  been  removed 
from  them  in  the  manner  above  indicated.  When  to  such  a 
solution  platinum  chloride,  acidified  with  some  hydrochloric  acid, 
is  added,  a  precipitate  ensues  which  is  insoluble  on  boiling.  In 
solution  there  remains  a  body,  which  I  have  termed  Isfarin,  and 
which  does  apparently  not  combine  with  platinum  chloride. 
Both  bodies,  assurin  and  istarin,  seem  to  have  some  attraction  for 
each  other,  like  sphingomyelin  and  kerasin,  which  causes  them  to 
crystallise  together,  so  as  to  represent  a  uniform  appearance  of 
star-shaped  masses  of  crystals.  This  union  is  apparently  never 
definite,  but  the  projDortions  of  the  ingredients  shift  according  to 
the  mass,  concentration,  and  temperature  of  the  solvents  used  for 
their  extraction.  On  the  whole,  frequent  recrystaUisation  from 
.spirit  causes  the  phosphorus  in  the  mixture  to  rise,  and  the  nitro- 
gen to  sink  relatively  to  the  phosphorus.  But  the  principle  here 
to  be  described  is  isolated  as  yet  only  by  platinum  chloride. 

Assurin  Hydrocldoraie  Flatiiium  Chloride. 
Yellow  crystalline  powder,  insoluble  in  boiling  spirit,  and  in 


Synopsis  of  the  Results  of  the  First  Series  of  Analyses  and  Theory. 


^At.  Wgts. 


Organ.  MolecL 

































These  data  lead  to  a  formula  2(C,^H9^N,P209HCI)PtCl,. 

Synojjsis  of  the  Results  of  the  Second  Series  of  Analyses  and  Theory. 


-f  At.  Wgts. 

-f  Pt  =  l. 

Organ.  Molecle. 



































0  269 


These  data  lead  to  a  formula  2(C^J4ioiN2PoOn^iCl)PtCl^, 
which  differs  a  little  from  the  former  one,  but  phosphorus  remains 
slightly  exceeding,  nitrogen  below  the  theory  derived  from  the 
p)latinum  chloride  as  starting  base.  Assuming  nitrogen  at  two 
atoms,  we  come  to  nearly  50  C,  but  encounter  again  an  excess  of 
10  per  cent,  in  the  phosphorus.  But  the  great  features  of  the 
results  of  the  quantations  are  evident.  We  have  to  deal  with  a 
phosphatide  in  which  the  radicle  of  phosphoric  acid  is  contained 
twice,  and  which  we  may  therefore  term  a  dii:)hosphatide.  In  this 
principle  there  are  contained  two  atoms  of  nitrogen,  which,  from 
analogy  with  other  phosphorised  bodies,  we  may  suppose  to  be 
contained  in  two  different  nitrogenised  radicles.  But  even  if  the 
two  atoms  of  nitrogen  were  contained  in  one  and  the  same  radicle, 
it  would  still  be  perfectly  correct  to  term  the  principle  a  dinitro- 
genised  diphosphatide.  For  the  nitrogen,  although  somewhat 
deficient  in  both  sets  of  analyses,  amounts  nevertheless  to  3*77 
molecles  in  the  latter  and  to  3*95  in  the  first  set  of  quantations 
when  compared  to  platinum  as  1. 

The  companion  of  assurin,  the  above-mentioned  istarin,  is  not 
X)hosphorised,  but  it  is  very  difficult  to  prepare  it  free  from  the 
last  traces  of  phosphorus.    Its  chemical  composition  is  expressed 


approximately  by  the  formula  C^QHg.,NO^  ;  it  therefore  seems  to 
belong  to  the  group  of  nitrogenised  fats  to  be  described  below. 
I  have  prepared  and  analysed  many  specimens  which  have  shown 
the  way  to  the  ultimate  complete  chemical  individualisation  of 
the  substance.  But  there  has  not  been  time  for  the  carrying  out 
of  the  laborious  operations  which  are  necessary  for  the  isolation 
of  the  quantities  required.  For  it  must  be  borne  in  mind  that 
befoi^e  istarin  is  reached  in  a  systematic  course  of  brain  analysis 
all  the  other  substances  described  previously  must  have  been 
removed  out  of  the  solution,  as  well  as  the  residues  of  the  solvents 
and  precipitants. 


Eocli/  from  Group  of  Cerehrlnacides. 

Such  a  principle  I  shall  have  to  describe  under  the  subgroup 
of  the  cerebrinacides,  amongst  which  it  occurs,  and  from  which 
it  has  not  yet  been  entirely  isolated.  Indeed,  it  may  be  ques- 
tioned w^hether  this  cerebrosulphatide  contains  phosphorus  as  a 
constituent  element,  or  only  as  a  constituent  element  of  an  ad- 
mixture. The  observation,  such  as  it  is,  is  too  important  to  be 
left  out  of  sight ;  and,  on  the  other  hand,  nothing  but  a  research 
of  great  dimensions  will  be  the  means  of  evolving  the  final  truth 
contained  in  it. 


A  body  typical  of  this  subgroup  was  discovered  by  limited 
chemolysis  of  kephalin,  as  descril^ed  in  the  chapter  relating 
thereto,  under  kephalophosphoric  acid.  Two  other  bodies  of  this 
kind  were  found  in  a  lead  precipitate  from  buttery  matter.  One 
was  a  crystallised  acid,  the  other  noncrystallised.  There  has  not 
been  time  for  advancing  the  knowledge  concerning  them ;  par- 
ticularly the  proof  is  yet  wanting  that  they  are  educts,  and  not, 
like  kephalophosphoric  acid,  products.  They  are,  therefore,, 
registered  here  mainly  as  objects  for  future  research. 

First  acid  from  buttery  matter. 
Second  ncid  from  buttery  matter. 
Kephalophosphoric  acid  (product). 


From  the  mixture  of  the  first  two  acids  a  barium  salt  sohihle 
in  ether  was  obtained,  reminding  of  the  bearing  of  the  kephahn 
and  sphingomyelin  series,  which  alone,  as  thus  far  known,  yield 
barium  salts  soluble  in  ether. 


PhosjjJiatide  of  the  Milk,  Ladophosphaticlc,  Casein. 

According  to  the  latest  researches,  casein  from  cows'  milk  has 
the  following  percentic  composition  : 

-f-  At.  Wgts.  Atoms. 

C  52-96  4-413  197-8 

H  7-05  7-05  316- 

N  15-65  1-1178  50- 

S  0-716  0-0223  1- 

P  0  847  0-0273  1-224 

O  22-78  1-4237  63-8 

It  will  be  seen  that  what  has  often  been  maintained  before  is 
here  again  propounded — namely,  that  a  substance  believed  to  be 
truly  albuminous  contains  not  only  sulphur,  but  also  phosphorus, 
as  an  essential  constituent.  On  general  grounds  I  think  this  very 
23robable.  Indeed,  the  phosphatides  of  the  brain  have  some  pro- 
perties which  are  so  much  like  those  of  casein  that  former 
inquirers  were  led  by  them  to  the  belief  that  the  brain  did 
actually  contain  casein.  As  casein  yields  by  chemolysis  about 
4*12  per  cent,  of  tyrosin,  and  as  the  atomic  weight  of  the  latter 
is  181,  the  atomic  weight  of  casein  must  be  at  least  4393.  Now 
if  casein  contained  one  atom  of  sulphur,  its  atomic  weight  would 
thereby  be  fixed  at  about  4469,  which  does  not  differ  much  from 
the  number  derived  from  the  tyrosin  ;  but  the  phosphorus  leads 
to  a  lower  number — namely,  3659.  Seeing,  however,  that  phos- 
phorus is  analytically  always  found  a  little  too  high,  we  need  not 
at  first  sight  attribute  too  much  importance  to  this  difference. 
Seeing,  on  the  other  hand,  that  albumen  contains  at  least  three 
atoms  of  sulphur,  we  need  not  despair  of  finding,  by  further 
inquiry,  a  better  ratio  between  the  phosphorus  and  sulphur  in 
casein  than  that  which  is  at  present  apparent. 


Phosphatides  of  the  Bile,  Cholophosphatides, 
It  is  generally  assumed  that  the  bile  contains  lecithin.  This 
^issumption  is  based  upon  the  fact  that  ox-bile,  by  chemolysis 
with  barita,  yields  fatty  acids  and  neurin.  Indeed,  neurin  was 
first  discovered  in  the  bile,  and  originally  termed  choHn.  I  have 
made  some  experiments  regarding  this  question,  and  come  to  the 
result  that  ox-bile  does  not  contain  lecithin,  but  contains  a  phos- 
phatide which,  to  conclude  from  its  crystallising  as  platinum 
chloride  salt,  seems  to  have  a  very  complicated  composition.  The 
formula  expressing  the  composition  of  the  platinum  chloride  com- 
pound with  P  =  1  was  Cg2Hi^^N^P03g,HCl  +  2PtCl^.  The  fact  that 
bile,  a  secretion  which  serves  the  chemistry  of  digestion  and 
■assimilation,  contains,  besides  its  specific  ingredients,  bodies 
which,  like  cholesterin,  are  identical  with  important  ingredients 
of  the  brain,  or,  like  this  cholophosphatide,  are  analogous  to 
them,  shows  that  the  biolytic  or  biosynthetic  process  which  leads 
to  the  formation  of  bile  is  much  more  complicated  than  has 
liitherto  been  supposed.  One  of  the  principal  fatty  acids  in  the 
bovine  cholophosphatide  is  stearic. 

Fhosjihafides  of  the  Blood,  Heinatophosphatides. 

A  phosphatide  was  found  mixed  with  a  preparation  of  hemine 
crystals  made  according  to  Eollet's  prescription.  It  was  extracted 
by  benzol  and  acetic  acid,  and  from  the  residue  of  this  solution 
by  hot  absolute  alcohol.  From  this  solution  it  was  precipitated 
as  CdCl^  salt ;  the  white  salt  was  recrystallised  and  analysed.  It 
led  to  an  empirical  formula,  C-(3Hj,5^N.,P^Oi4  + 2CdCl^.  From  this 
it  is  probable  that  the  salt  was  a  mixture  of  a  mononitrogenised 
with  a  dinitrogenised  phosphatide — if  a  conclusion  may  be  drawn 
from  its  physical  appearance,  paramyelin  and  amidomyelin.  It 
had  almost  the  same  percentic  composition  as  a  similar  prepara- 
tion of  a  CdCl^  salt  obtained  from  brain.  We  may  assume  that 
this  phosphatide  came  from  the  blood-corpuscles,  like  the  hematin 
which  it  accompanied,  and  was  an  element  of  their  bioplastic 
constitution.  Whether  it  was  in  any  way  centralised,  like  the 
phosj^hatides  of  cell-nuclei,  cannot  be  stated. 

From  an  ether  extract  of  blood-corpuscles  of  the  ox  I  obtained 
a  cadmium  chloride  precipitate,  of  which  a  portion  was  soluble  in 
cold  benzol — lecithin  cadmium  chloride;  while  another  portion 
was  insoluble  in  boiling  benzol — amidomyelin  cadmium  chloride. 


Phosphatides  of  Nucleolar  Centres  of  Growth  [Bioj^lasm,  Cells,  etc.), 

Aggregations  of  cells,  whether  vegetable,  such  as  yeast,  or 
animal,  such  as  sperma,  pus,  or  liver  (the  latter  after  removal  of 
bloodvessels  and  connective-tissue),  are  known  to  contain  a 
peculiar  phosphorised  substance.  As  this  substance  was  supposed 
to  be  contained  in  or  to  constitute  the  nucleus,  it  was  called 
nuclein.  This  term  would  be  unobjectionable  if  all  tissue 
elements  yielding  the  substance  contained  nuclei.  However,  for 
our  present  purpose  we  will  consider  mainly  those  which  do 
contain  nuclei,  and  leave  the  others  for  future  consideration. 

The  nucleolar  matter  has  mostl}^  been  obtained  by  subjecting 
the  cells  to  a  process  of  artificial  digestion.  The  undigested 
(i.e.,  undissolved)  part  was  supposed  to  be  unaltered  nucleolar 
matter.  This  was  now  extracted  with  dilute  caustic  alkali,  and 
from  the  filtered  solution  the  nuclein  so-called  was  precipitated 
by  dilute  hydrochloric  acid.  This  was  washed  with  alcohol  and 
ether,  dried  in  vacuo,  and  analysed.  Other  authors  avoided  the 
process  of  digestion,  and  extracted  the  mass  of  cells,  such  as 
German  yeast,  with  soda  lye  directly,  and  treated  the  filtrate  as 
just  described.  Nuclein  from  yeast  thus  obtained  gave  from 
40-42  to  41-22  per  cent,  of  C,  5-15  to  5-52  per  cent.  H,  15-31  to 
15-99  per  cent.  N,  6*1  to  6-29  per  cent.  P,  and  0-38  to  0-41  per 
cent.  S  ;  or — ■ 

C  40-81 
H         5  -38  • 
N  15-76 
P  6-19 
S  0-39 

But  a  great  number  of  other  analyses  gave  only  from  2-58  to 
3-98  per  cent.  P.  The  nuclein  from  pus-corpuscles  gave  from 
2-28  to  2*62  per  cent.  P,  about  1-7  per  cent.  S,  and  from  14  to 
15-02  per  cent.  N,  besides  49-58  per  cent.  C,  and  7*10  per  cent.  H. 
Nuclein  from  the  red  blood-corpuscles  from  geese  gave  6*04  to 
7-12  per  cent.  P,  and  0-4  per  cent.  S;  while  so-called  nuclein 
from  the  so-called  nucleolar  formations  of  the  yelk  gave  7-10  per 
cent.  P,  0-99  per  cent.  S,  and  13-46  per  cent.  N. 

From  this  it  will  be  evident  that  the  science  of  the  nucleins 
is  only  in  course  of  development,  and  that  there  are  at  present 


two  groups  of  these  substances  known — one  with  from  6  to  7  per 
cent.  P,  another  Avith  from  2  to  3  per  cent.  P.  The  latter  is  the 
better  known.  It  yields,  by  long  boiling  with  water,  p]ios])1wric 
acid,  an  albuminous  suhtafice  soluble  in  water,  and  a  peptone,  and 
a  mixture  of  the  three  alkaloids,  hy]Joxanthin,  xanthin,  and  guanin. 
From  the  study  of  the  phosphatides  of  the  brain,  we  can  have  no 
difficulty  in  explaining  such  a  body  hypothetically  to  be  a  phos- 
phatide. The  body  with  the  high  amount  of  phosphorus  we  could 
comprehend  to  be  a  di-  or  triphosphatide ;  whereas  the  body  with 
the  lesser  amount  of  P  would  have  a  more  simple  structure. 
However,  our  only  object  in  this  place  is  to  direct  attention  to 
these  bodies  also  ;  for  there  can  be  no  doubt  that  the  knowledge 
of  each  set  of  organic  principles  will  enable  us  to  advance  that  of 
the  others. 


The  phosphatides,  as  they  exist  in  brain-matter,  and  as  isolated 
therefrom,  are  associated  with  certain  bases,  by  a  power  of  com- 
bination derived  from  their  acid  character.  These  bases  can  only 
b)e  removed  and  the  principles  obtained  in  a  pure  state  by  dis- 
solving the  compounds  in  water,  and  adding  hj^drochloric  acid, 
which  combines  loosely  with  the  principles  on  account  of  their 
alkaloidal  character,  to  the  exclusion  of  the  bases,  which  then 
pass  into  solution  as  chlorides. 

In  order  to  obtain  some  knowledge  regarding  the  relative 
amounts  and  nature  of  the  bases  in  combination  with  the  phos- 
phorised  constituents  of  brain-matter,  a  quantity  of  solution 
obtained  by  the  hydrochloric  acid  process,  above  described,  and 
which  was  derived  from  kephalin,  paramyelin,  and  lecithin,  was 
submitted  to  analysis. 

It  was  evaporated  to  dryness,  and  the  residue  ignited  in  a  pre- 
viously weighed  platinum  dish.  During  this  ignition  much 
chloride  of  ammonium  was  given  out,  and  its  nature  distinctly 
proved  by  condensing  and  analysing  it. 

The  fused  mass  was  dissolved  in  dilute  hydrochloric  acid,  and 
the  solution  so  obtained  treated  with  excess  of  ammonia.  The 
white  gelatinous  precipitate  which  was  thrown  down  was  scarcely 
coloured  black  by  sulphide  of  ammonium.  The  precipitate  and 
filtrate  were  submitted  to  qualitative  and  quantitative  analysis. 


The  Precipitate. — The  colouring-matter  was  evidently  sulphide 
of  iron,  but  it  did  not  amount  to  more  than  a  trace.  [The  original 
solution  had  been  subjected  in  a  neutral  state  to  a  current  of  sul- 
phuretted hydrogen  with  the  object  of  removing  some  platinum 
that  had  been  used  along  with  the  hydrochloric  acid,  as  PtCl^,  in 
the  precipitation  of  the  kephalin  and  myelin  from  the  aqueous 
solutions.  This  treatment  must,  therefore,  have  removed  any 
copper  and  iron  which  were  undoubtedly  present.] 

The  precipitate  was  dissolved  in  dilute  hydrochloric  acid,  and 
the  calcium,  magnesium,  and  phosphoric  acid  estimated  as 
follows  : 

The  solution  was  nearly  neutralised  by  sodic  carbonate,  after 
addition  of  some  ferric  chloride,  and  then  an  excess  of  pure 
baritic  carbonate  was  added  ;  the  mixture  was  shaken,  allowed  to 
stand,  and  then  filtered. 

From  the  concentrated  filtrate  the  barium  was  removed  by  sul- 
phuric acid,  and  the  filtrate  was  then  precipitated  in  the  presence 
of  ammonia  by  oxalate  of  ammonium.  The  oxalate  so  obtained 
was  converted  by  intense  ignition  into  oxide,  CaO,  which  weighed 
0-1994  g.=  0-1423  g.  calcium. 

The  filtrate  and  washings  from  the  calcium  oxalate  were  treated 
as  ordinarily  in  cases  where  it  is  desired  to  estimate  magnesium, 
and  there  was  obtained  0*5555  g.  ^i^.^fiy,  =  0*1212  g.  mag- 

The  precipitate  which  had  been  produced  by  ferric  chloride 
and  sodium  and  barium  carbonates  was  dissolved  in  nitric  acid, 
and  the  phosphorus  estimated  by  the  combined  molybdate  and 
magnesium  methods.  This  gave  0'3266  g.  phosphorus  =  0*7480  g. 
phosphoric  acid  (P2^5)- 

The  A'mmoniacal  Filtrate. — This  was  proved  to  be  free  from  mag- 
nesium and  calcium.  The  potassium  contained  in  it  was  estimated 
in  the  usual  way  by  means  of  platinic  chloride,  giving  11*2766  g. 
of  2KCl,PtCl4  salt=  3*651  g.  KCl  =  1*911  g.  potassium.  The 
mother-liquor  and  washings  were  evaporated  to  drj^ness,  and  the 
platinum  was  removed  by  extracting  the  ignited  mass  with  water 
acidified  by  hydrochloric  acid.  The  extract  so  obtained  was 
evaporated  to  dryness  and  fused  ;  the  residue  weighed  3*45  g. 
(NaCl)  =  1*356  g.  sodium.  The  quantities  of  potassium  and 
sodium  thus  found  were  controlled  by  the  analysis  of  a  separate 
part  of  the  original  solution  containing  their  chlorides,  and  cal- 


dilating  from  the  residue  obtained  on  evaporation,  there  should 
have  been  found  : 

A  total  quantity  of  chlorides  =  7 '09  g. 

There  was  found    -       KCl  =  3  -6  5 1 
and  NaCl=  3-450 

or  a  total  of  =  7 '101  „ 

Distribution  of  the  Bases  and  Phosphoric  Acid. — Assuming  the 
calcium  and  magnesium  to  have  originally  existed  as  tribasic 
phosphates,  and  any  phosphoric  acid  remaining  over  to  have  been 
in  combination  with  potassium,  then  we  have  : 

Ca  =0-1423  g.  existing  as  SCaO,?^,. 
Mg  =  0-1212  „       „  3MgO,PA. 
K  =0-5663  „       „  3K,0,P205- 
K  =1-3447  „  I  combined  directly  with  kephalin, 

Na  =1-356    „  j     pararayelin,  and  lecithin. 

P   =0-3266,,       „         P2O5  (0-748  g.)  and  distributed 

between  the  Ca,  Mg,  and  K. 

It  has  been  proved  above  that  kephalin  was  partly  in  combina- 
tion with  calcium  oxide,  or  lime,  uncombined  with  any  other 
acid.  In  the  present  research  we  find  that  there  may  be  in 
kephalin  (and  myelin)  even  a  much  greater  quantity  of  potash 
and  soda  in  direct  combination  than  of  lime.  Both  observations 
supplement  each  other,  the  first  one  being  qualitative  only,  the 
present  one  stating  the  quantities  of  the  bases  relatively  to  each 


Glycerophosphate  of  lead  may  be  prepared  from  the  solution  of 
barium  glycerophosphate  as  obtained  by  the  chemolysis  of 
phosphorised  matters,  by  j^recipitation  with  any  soluble  salt  of 
lead,  as,  for  example,  the  chloride  or  acetate.  In  order  to  entirely 
remove  glyccrophosphoric  acid  in  this  way  from  the  solution,  it  is 
necessary  to  concentrate  and  neutralise  the  latter  from  time  to 
timei,  on  account  of  a  slight  solubility  of  the  glycerophosphate  of 

Glyceroi)hosphate  of  lead  prepared  synthetically  is  granular 
and  white,  and  remains  so  on  drying,  whereas  when  it  is  obtained 


from  kephalin  it  dries  to  a  hard,  brittle,  slightly  coloured  mass, 
even  when  chemically  pure. 

On  ignition,  the  salt  leaves  a  residue  of  pyrophosphate  of  lead, 
and  this  offers  a  ready  means  of  ascertaining  the  purity  of  the 
preparation.  Thus,  with  a  specimen  of  the  salt  jDrepared  as 
described  from  kephalin,  it  was  found  that  0-911  g.  left  a  residue 
of  0-744  g.  Pb^PoO^,  while  theory  requires  0-7104  g. 

Glyceroi?liosplmte  of  calcium  (normal  salt)  may  be  prepared  from 
the  lead  salt  by  decomposition  with  hydrothion,  and  neutralisation 
of  the  filtrate  with  calcium  carbonate. 

This  salt  is  much  less  soluble  in  a  hot  concentrated  aqueous 
solution  than  in  the  same  amount  of  water  in  the  cold.  It  is 
therefore  best  isolated  by  filtration  of  a  precipitate  from  the 
nearly  boiling  solution. 

A  quantity  of  the  lead  salt,  referred  to  above,  was  converted 
into  calcium  salt,  and  the  solution  evaporated  near  the  boiling- 
point,  when  a  w^hite  deposit  of  calcium  glycerophosphate  formed. 
This,  when  washed  and  dried,  was  analysed.  0-3400  g.,  after 
strong  ignition  with  the  aid  of  nitric  acid,  left  a  residue  of 
0-207  g.,  equal  to  60  8  per  cent.  Ca^PgO^.  Pure  calcium  glycero- 
phosphate should  leave  60-5  per  cent,  pyrophosphate. 

Another  sample  of  the  calcium  salt  prepared  as  described  gave 
the  following  figures  on  analysis  : 

which  shows  the  composition  of  this  salt  to  be  according  to  the 
formula  CgH.CaPO,. 

Acid  Glyccropliospliate  of  Calcium. — A  solution  of  the  calcium 
salt  neutral  to  test-paper  becomes  on  heating,  and  at  the  same 
time  as  the  normal  salt  separates,  acid  to  test-paper ;  and  if 
the  mother-liquor  is  now  precipitated  with  alcohol,  there  is  pro- 
duced, not  the  normal  but  the  acid  salt.  A  portion  precipitated 
in  this  way  by  alcohol  was  white  and  granular.  It  was  dried 
at  100°  C. 

0-827  g.  left  on  ignition  0-478  g.  residue  =  57-80  per  cent.  Now 
the  normal  salt  would  have  given,  as  we  have  seen,  60-5  per 










cent,  residue.  This  observation  led  to  the  theory  of  an  acid  salt 
of  this  construction,  C3H^CaPOg,C3H9PO,3,  giving  a  total  formula 
of  C^3HJgCaP20^2 ;  and  it  was  probable  that  on  ignition  such  a 
salt  would  leave  a  residue  of  half-saturated  acid  pyrophosphate 
H.CaP.O^,  losing  only  CeHi.O^. 

On  this  theory,  the  residue  should  have  amounted  to  56-54  per 
cent.  ;  it  did  amount  to  57*80  per  cent. 

Gli/cerophosjjhate  of  harium  prepared  from  synthetically  made 
acid  and  barium  carbonate  was  white,  and  behaved,  as  regards  its 
insolubility  in,  and  consequent  precipitation  from  hot  aqueous 
solution,  similarly  to  the  calcium  salt.  But  this  property  of 
separation  of  the  salt  on  boiling  the  solution  seemed  to  be  only 
transient,  for  after  a  solution  had  stood  for  sixteen  hours  after  it  had 
been  so  precipitated,  no  precipitation  occurred  on  again  boiling  the 
solution,  and  ammonia  produced  a  voluminous  precipitate  in  the 
solution,  apparently  indicating  that  a  partial  decomposition  of  the 
salt  had  occurred. 

Some  of  the  salt  was  prepared  from  the  solution  resulting  from 
the  decomposition  of  kephalin  by  barita,  by  precipitation  with 
alcohol.  This  was  redissolved  in  water,  and  reprecipitated  by 
alcohol  several  limes;  finally  it  was  dissolved  in  water,  and  con- 
centrated by  evaporation  on  the  water-bath,  when  a  deposit 
occurred.  This  was  isolated,  dried  by  pressure  between  folds  of 
paper,  and  over  H2SO4  in  vacuo,  and  finally  at  100°  C.  At  110"  C. 
it  was  not  afiected ;  it  was  now  analysed. 

leading  to  formula  C3HH,BaP0^. 

Another  specimen  of  barium  glycerophosphate  was  prepared 
much  in  the  same  way,  but  with  this  difference,  that  whereas  the 
one,  the  analysis  of  which  has  just  been  given,  was  separated 
from  water  by  boiling,  the  one  now  to  be  described  was  precipi- 
tated from  aqueous  solution  by  alcohol,  with  which  it  was  also 
washed.  On  isolation  the  precipitate  contracted,  became  horny, 
transparent,  and  finally  fused  to  a  thick  liquid.  It  eventually 
dried  to  a  brittle  mass.    On  analysis  it  gave  : 











C  =  12-611 
H  =  2-933 
Ba  =  40-950 
P  =  9-266 
0     =  34-240 

leading  to  formula  OgH^BaPOgjH^O. 

These  observations  led  to  the  surmise  that  the  barium  salt  as 
precipitated  by  alcohol  was  a  true  alcoholate.  The  truth  of  this 
hypothesis  was  proved  by  the  experiments  now  to  be  described. 

The  Alcoliolo-liydrated  Barium  Glyceroj)hosphate. — A  quantity  of 
barium  glycerophosphate,  as  prepared  by  the  chemolysis  of 
kephalin  with  barita,  was  precipitated  by  alcohol,  and  the  pre- 
cipitate washed  with  alcohol,  after  which  it  was  exposed  to  the 
air,  when  it  lost  alcohol,  became  brown  and  somewhat  brittle 
round  the  edges,  and  began  to  fuse.  At  this  stage  it  was  again 
dissolved  in  the  minimum  amount  of  cold  water,  and  the  solution 
reprecipitated  by  absolute  alcohol.  The  precipitate  so  prepared 
was  isolated  and  allowed  to  drain.  When  thoroughly  drained,  a 
small  quantity  was  pressed  in  a  vice  between  folds  of  blotting- 
paper,  until  it  became  pulverulent.  It  was  now  heated  in  an  air- 
bath  at  100°  C,  until  it  was  approximately  dry.  In  this  way 
0-7354  g.  lost  0-237  g.  and  became  0*4978  g.,  corresponding  to  a 
loss  of  32-30  per  cent.  The  residue  of  this  operation,  when  burnt, 
left  a  residue  weighing  0*3064  g.,  equal  to  61-5  per  cent. 

Pure  normal  barium  glycerophosphate  leaves  on  ignition  72*96 
per  cent,  residue,  while  the  hypothetical  acid  salt  of  formula 
C3H7BaPO^,C3HgPO,3,  might  presumably  leave  under  such  con- 
ditions 65*3  per  cent,  of  H2BaP20^. 

A  salt  of  the  formula  qI^jj'^^pq*"  |  -^2^  would  leave  on  igni- 
tion 62*9  per  cent.  H^BagPO^. 

After  this  preliminary  experiment,  the  whole  precipitate  ob- 
tained by  alcohol,  amounting  to  71  g.,  was  dried  by  pressure 
between  folds  of  paper,  until  it  was  quite  pulverulent.  It  was 
then  placed  in  200  cc.  water,  in  which  it  set  like  glue,  but  after 
forty- eight  hours  had  not  entirely  dissolved.  An  addition,  however, 
of  100  cc.  more  water  produced  a  perfect  solution.  This  was  now 
subjected  to  distillation,  and  the  alcohol  contained  in  the  first 
150  cc.  distillate  determined.  It  was  thus  shown  that  in  the  71  g. 
of  glycerophosphate,  which  had  been  so  dry  that  it  could  be 



powdered,  there  were  14-84  g.  of  absolute  alcohol,  or  20-9  j^er 

The  analytical  results  show  : 

Absolute  ethylic  alcohol  -  -  -  20-9 
Water    -  11-4 

Total  volatile  at  100°  C. 

Eesidue  of  barium  phosphate  - 
Volatile  at  red  heat 

Total  glycerophosphate  of  Ba  - 

-  32-3 

-  41-6  (form  undetermined.) 

-  26-1 

-  67-7 



There  are  probably  at  least  three  molecles  of  alcohol  and  six 
of  water  combined  with  one  molecle  of  acid  glycerophosphate  in 
this  compound."^ 

The  residue,  from  which  the  alcohol  had  been  distilled,  was 
concentrated  by  evaporation  on  a  water-bath,  when  it  deposited 
granular  matter,  which  on  analysis  was  found  to  be  normal  gly- 
cerophosphate of  barium,  CgH^BaPO^^. 

The  mother-liquor  obtained  after  the  separation  of  the  normal 
barium  salt  just  alluded  to,  was  again  precipitated  by  absolute 
alcohoL  The  precipitate  was  dried  by  jjressure  between  folds  of 
paper  until  it  was  pulverulent.  It  now  w^eighed  63  g.,  and  was 
dissolved  in  300  cc.  water,  and  the  solution  distilled  to  one-half. 
On  estimation  of  the  alcohol,  it  was  found  that  the  salt  had  con- 
tained 15*5  per  cent,  absolute  alcohol. 

Finally  the  residual  solution  of  barium  glycerophosphate  was 
transformed  into  lead  salt,  and  the  lead  salt  into  calcium  salt. 
That  portion  of  the  calcium  salt  which  was  deposited  from  a 
boiling  solution  was  found  to  be  normal.  From  the  mother- 
liquor,  which  grew  acid,  a  salt  was  precipitated  by  alcohol,  which, 
from  a  determination  of  the  residue  left  on  combustion  of  a  por- 
tion of  it,  seemed  to  be  the  acid  salt  of  calcium. 

'•■  The  salts  of  kryptophanic  acid  (from  urine)  and  kreatylic  acid  (from 
flesh)  present  characters  which  recall  those  of  glycerophosphate  of  barium. 
Thus  the  copper  salt  of  kryptophanic  acid,  when  precipitated  by  alcohol, 
behaves  like  the  glycerophosphate  of  barium  already  described,  yielding,  on 
distillation  with  water,  alcohol. 

The  f»jll()wing  alcoliolates  of  inorganic  salts  are  known  :  ZnCl2,2C2HgO  ;. 
CaCl,,4aHoO  ;  Mg(N()3),„6C,,H60  ;  etc. 


Barium  glycerophosphate  in  a  concentrated  syrupy  sokition  in 
water,  when  allowed  to  stand  in  a  covered  deep  vessel,  crystallizes, 
after  the  lapse  of  a  very  long  time,  in  radiary  masses  of  needles. 

Glycerophosphate  of  barium,  not  only  seems  to  be  the  only 
organic  compound  which  is  known  to  form  alcoholates,  but  it  is 
also  in  so  far  unique,  as  it  forms  an  alcoholate  and  a  hydrate  at  the 
same  time. 

The  differences  observed  in  the  relative  amounts  of  alcohol  and 
water  may  be  caused  by  the  different  proportions  of  these  bodies 
which  are  present  at  the  moment  of  precipitation.  If  several 
alcoholo-hydrates  are  producible,  the  method  of  preparation  makes 
it  unavoidable  that  a  mixture  of  these  should  be  produced.  But 
even  if  this  were  not  the  case,  and  if  there  were  only  one  type  of 
alcoholo-hydrate,  the  varying  amounts  of  alcohol  in  different  pre- 
cipitations would  compel  us  to  assume  that  alcohol  and  water 
may  substitute  each  other  in  indefinite  proportions,  as  isomor- 
phous  compounds  do  in  mixed  crystals. 

The  insoluble  lead  salt  is  very  stable  ;  next  comes  the  calcium 
salt,  then  the  barium  salt. 

Other  salts,  such  as  those  of  silver  and  copper,  seem  to  decom- 
pose at  every  stage  of  their  production,  so  that  although  volumi- 
nous at  first,  they  fall  away  to  almost  nothing  during  attempts 
at  their  purification. 

During  all  transformations  or  concentrations  of  solutions,  con- 
siderable quantities  of  the  acid  are  decomposed,  and  the  relative 
phosphates  and  glycerol  are  formed. 





General  Proioerties  of  the  Stihgrovp. 

The  cerebrosides  are  all  white,  and  more  or  less  opaque,  but 
are  capable  of  becoming  in  part  transparent  like  wax.  They  are 
deposited  from  hot  alcoholic  solutions  in  minute  microscopic 
particles,  which  may  be  termed  crystalline,  but  have  no  claim  to 
be  termed  crystallised.  These  particles  are  arranged  in  various 
composite  forms — balls,  or  branched  masses,  or  rosettes  ;  the 
latter  will  be  more  fully  described  under  the  headings  referring 
to  the  several  varieties. 

The  cerebrosides  are  all  soluble  in  hot  alcohol,  particularly 
absolute  alcohol,  and  deposited  on  cooling ;  they  are  very  little 
soluble  in  cold  absolute  alcohol,  much  less  soluble,  indeed,  than 
sphingomyelin,  which  can  thus  be  separated  from  the  bulk  of  the 
cerebrins.  The  mixture  is  dissolved  in  hot  alcohol  and  allowed 
to  cool ;  nearly  all  the  cerebrin  bodies  fall  down ;  much  sphingo- 
myelin remains  in  solution.  The  deposit  is  separated  from  the 
liquid  and  subjected  to  this  treatment  until  the  mother-liquor  is 
free  from  phosphorus.  It  is  further  purified,  as  will  be  shown 
lower  down. 

The  cerebrosides  are  almost  insoluble  in  water.  One  g.  of  purified 
phrenosin  from  ox  was  powdered  and  boiled  in  100  cc.  of  water ; 
the  solution  was  filtered  through  force-filters,  and  of  the  filtrate 
50  cc.  were  evaporated  on  the  water-bath  to  dryness  in  a  platinum 
dish.  As  this  increased  in  weight  by  only  0-025  g.,  one  part  of 
this  phrenosin  was  soluble  in  2,000  parts  of  water.    Pure  phre- 


nosin  does  not  swell  on  being  boiled  with  water,  but  remains 
pulverulent  and  unaffected.  When  the  cerebrosides  swell  and 
become  starchy  in  hot  water,  they  contain  phosphorised  matter  as 
an  admixture. 

The  cerebrosides  are  quite  insoluble  in  cold  benzol.  They  swell 
in  it,  and  become  quite  transparent,  so  as  almost  to  disappear 
from  sight.  But  when  the  benzol  is  filtered  off  and  evaporated, 
it  does  not  leave  a  vestige  of  matter  behind.  But  in  hot  benzol 
the  cerebrosides  are  extremely  soluble,  and  on  cooling  are  de- 
posited as  a  gelatinous  mass,  which  requires  agitation  before  it 
can  be  filtered,  From  the  hot  solution  cold  alcohol  precipitates 
white  flakes.  This  treatment  facilitates  the  separation  of  the 
cerebrosides  from  the  benzol. 

The  cerebrosides  are  almost  insoluble  in  either  cold  or  hot 
ether,  and  are  by  this  solvent  purified  from  kephalin  and  its 
relations,  from  lecithin,  cholesterin,  from  krinosin  and  istarin. 
But  the  separation  from  myelin  and  sphingomyelin  cannot  be 
effected  so  easily  by  ether  as  by  the  absolute  alcohol  treatment 
above  described,  the  lead-jDrocess  to  be  described,  and  the  cadmic 
chloride  and  hydrothion  in  ethereal  solution  treatment  to  be 
described  lower  down. 

The  cerebrosides  behave  neutrally  towards  hydrothion,  whether 
they  are  suspended  in  alcohol  or  ether.  Any  metals  which  may 
be  combined  or  mixed  with  them  may  then  be  removed  as  sul- 
phides without  injury  to  the  cerebrosides.  They  are,  therefore, 
in  this  respect  unlike  some  of  the  phosphorised  principles,  which 
seem  to  combine  with  hydrothion,  and  are  with  its  aid  able  to 
retain  metallic  sulphides  in  solution  in  ether. 

The  mixture  of  cerebrosides  has  been  repeatedly  examined  as 
to  the  relative  amount  of  the  elements  of  which  it  is  constituted, 
and  there  have  been  found  in  percents.  : 
























A  certain  amount  of  sulphur  is  also  present  as  a  constituent  of 
a  subgroup,  which  will  be  described  lower  down. 

The  nitrogen  is  rarely  found  exceeding  3  per  cent.  ;  so  much 
as  4-4  per  cent,  has  been  found  only  once  in  my  researches,  and 
that  in  a  case  where  the  barita  process  had  been  used.    In  pro- 


cesses  in  which  barita  was  not  used,  the  cerebroside  mixture  con- 
tained from  2-4  to  3-2  per  cent,  of  nitrogen.  And  in  a  process 
Avhere  barita  had  been  used,  but  probably  in  a  lesser  quantity,  or 
with  less  effect,  only  2-2  per  cent,  of  nitrogen  was  retained  in 
the  cerebroside  mixture. 

].  Separation  of  the  Cerebroside  Principles  of  the  Brain. 

Spirit  Treatment. — The  white  matter  obtained  by  the  process 
described  above,  from  which  lecithin  and  kephalin  have  been 
removed  by  treatment  with  ether,  and  which  has  been  recrystal- 
lised  from  spirit  eight  several  times,  is  further  purified  as  follows  : 

The  mixture,  containing  phrenosin,  kerasin,  cerebrinic  acid, 
and  sphingomyelin,  is  brought  to  the  consistence  of  cream  by 
rubbing  in  a  mortar  with  spirit  of  85  per  cent.,  and  is  added  in 
small  quantities  at  a  time  to  hot  spirit  in  a  platinum  vessel. 
This  is  done  in  order  to  effect  as  perfect  a  solution  of  the  soluble 
part,  and  to  prevent  as  much  as  possible  the  formation  of  in- 
soluble matter.  The  solution  is  filtered  hot  and  set  aside  to 
deposit.  On  cooling  a  white  body  comes  down  and  is  collected. 
On  analysis  this  is  found  to  contain  about  0'856  per  cent,  of  phos- 
phorus. This  process  is  repeated  a  tenth  time,  and  the  product 
having  lost  only  little  of  the  phosphorised  ingredient  (which  in 
spirit  of  85  per  cent,  strength  has  the  same  solubility  as  the  cere- 
brin  bodies)  is  subjected  to  treatment  with  lead  acetate. 

Lead  Acetate  Treatment. — The  body  is  triturated  with  alcoholic 
solution  of  lead  acetate,  and  the  mixture  poured  as  before  into 
hot  spirit ;  the  solution  is  filtered  hot,  and  allowed  to  cool.  The 
deposit  is  collected,  and  treated  with  more  alcoholic  solution  of 
lead  acetate,  and  filtered  from  the  excess  of  liquid.  After  this  it 
is  twice  dissolved  in  hot  spirit  to  remove  excess  of  lead  acetate. 
The  deposit,  on  analysis,  is  found  to  contain  about  073  per  cent, 
of  phosphorus. 

The  body  is  now  triturated  with  icatery  solution  of  lead  acetate, 
and  pressed  to  remove  the  excess  of  liquid.  The  mass  is  made 
into  a  cream  with  cold  spirit,  and  added  in  small  quantities  to  hot 
spirit.  The  solution  is  filtered  and  set  aside  to  cool,  and  the 
stearoconotiscd  portion  is  put  aside  for  separate  treatment.  The 
alcoholic  and  watery  filtrates,  from  which  all  matters  deposited 
on  cooling  have  been  removed,  are  concentrated,  and  treated  as 
shall  be  described  elsewhere.    The  white  body  which  comes  down 


from  the  spirit  solution  on  cooling  is  collected  and  treated  again 
with  spirit,  and  this  process  is  repeated  until  no  more  so-called 
stearoconote  (or  lead  ^precipitate)  is  produced.  The  ultimate 
deposit  obtained,  after  all  these  recrystallisations  have  been 
carried  out,  is  collected  and  dried  at  100°  C.  At  this  temperature 
it  does  not  alter  in  appearance.  It  gives  the  purple  reaction  with 
oil  of  vitriol  alone,  and  on  analysis  is  found  to  contain  0*73  per 
■cent,  of  phosphorus. 

Lead  acetate,  without  ammonia,  as  here  applied,  precipitates 
almost  all  true  myelin,  besides  some  cerebrinic  acid  and  other 
matters.  To  purify  the  cerebrosicles  completely  from  matters  of 
this  class,  it  is  necessary  to  add  ammonia  to  the  lead  acetate. 
By  that  means  a  condition  of  the  alcoholic  solution  of  the  cerc- 
brosides  is  attained,  in  which  neither  lead  acetate,  nor  ammonia, 
nor  a  mixture  of  both  produces  any  further  precipitates.  Then 
the  solution  contains  mainly  phrenosin,  kerasiu,  krinosin,  and 
sphingomyelin,  which  are  deposited  on  cooling,  excepting  only 
some  kerasin  and  sphingomyelin,  which  .remain  in  solution. 

Absolute  Alcohol  Treatment  ivitliout  Fractionation  of  Precipitate. — 
Absolute  alcohol  is  now  used  in  place  of  spirit  of  85  per  cent., 
and  the  solution  and  recrystallisation  are  repeated  a  great  number 
of  times  until  the  rnother-liquors  gives  no  more  precipitate  with 
cadmic  chloride.  As  long  as  the  alcoholic  filtrate  gives  a  precipi- 
tate with  this  reagent  it  is  manifest  that  it  removes  the  phos- 
phorised  sphingomyelin,  and,  as  will  be  seen  below,  the  separation 
of  the  phosphorised  part  succeeds,  gradually  but  effectually,  to 
the  extent  of  concentrating  the  phosphorus  in  the  part  soluble  in 
the  cold,  so  that  it  contains  nearly  2  per  cent.  (1-951  per  cent.), 
while  the  part  insoluble  in  the  cold  retains  only  one-tenth  of  that 
amount.  But  when  the  solubility  of  the  phosphorised  ingredient 
in  absolute  alcohol  has  become  again  equal  to  that  of  the  nitro- 
genised  substance,  it  is  found  requisite  to  resort  to  fractional 
precipitation  for  the  purpose  of  isolating  pure  educts. 

Separation  of  Phrenosin  and  Kerasin  by  Fractional  Precipitation  on 
Cooling. — When  the  absolute  alcohol  solution  begins  to  deposit 
matter,  which  occurs  between  50'  and  40°,  rosettes  of  phrenosin 
appear  first.  When  the  temperature  reaches  28°  this  ceases ;  and 
the  supernatant  liquor  is  clear  for  a  while  until  the  temperature 
falls  to  26°.  Below  this  tempei'ature  a  gelatinous  cloudy  mass, 
mainly  of  kerasin,  gradually  forms  and  floats  on  the  phrenosin. 


The  phrenosin  is  therefore  isolated  as  follows.  When  the 
temperature  of  the  liquid  in  which  the  phrenosin  crystallises  has 
fallen  to  28°,  the  mother-liquor  which  contains  most  of  the  kerasin 
in  solution  is  swiftly  decanted,  either  with  or  without  the  employ- 
ment of  a  filter  kept  at  28°  by  a  water-bath  ;  and  the  phrenosin 
is  thus  recrystallised  seven  times  until  no  further  separation  seems 
to  be  effected. 

An  analysis  of  a  large  specimen  of  phrenosin  at  this  stage  gave 
phosphorus  equal  to  0-182  per  cent.,  and  after  two  further  treat- 
ments in  the  same  way  it  yielded  phosphorus  equal  to  0*1 13  per 
cent.  It  also  gave  in  two  estimations  the  following  quantities  of 
inorganic  matter  :  (I.)  =0=19  per  cent.  ;  (II.)  =  0-23  per  cent.,  con- 
taining "07  of  potash  (KgO).  The  dried  kerasin  yielded  phos- 
phorus =  0*198  2)er  cent,  and  potash  =0-07,  from  which  it  will  be 
seen  that  the  many  resolutions  and  the  several  lead-treatments 
had  not  yet  removed  all  inorganic  ingredients  from  these  matters. 

2.  Phrenosin  and  its  Derivates. 

a.  Further  Purification  of  Phrenosin  hij  Cadmic  Chloride,  Ether,  and 


The  phrenosin  isolated  by  fractional  precipitation  as  described 
above  is  mixed  with  solution  of  cadmic  chloride,  and  the 
mixture  suspended  in  ether.  Hydrothion  is  j)assed  into  this, 
when  a  yellow  solution  and  a  yellow  precipitate  form,  which 
remain  mixed  with  the  bulk  of  the  undissolved  phrenosin.  The 
solid  matter  is  filtered  from  the  liquid  ;  it  consists  of  phrenosin 
and  cadmic  sulphide,  while  a  peculiar  compound  of  a  phosphorised 
body  with  cadmic  sulphide  remains  in  solution.  The  residue  is 
removed  from  the.  filter  and  dissolved  in  hot  85  per  cent,  spirit. 
The  insoluble  cadmic  sulphide  is  filtered  off,  and  the  solution  is 
set  aside  to  deposit.  On  cooling  phrenosin  comes  down  in  large 
rosettes,  and  is  collected  and  recrystallised,  first  twice  from  85 
jDer  cent,  spirit,  and  finally  from  absolute  alcohol.  It  is  dried^ 
and  then  exhibits  the  following  properties.  When  boiled  with 
water  it  does  not  swell  to  a  starchy  paste,  but  merely  becomes 
flocculent  and  floats  about  in  the  fluid.  Treated  by  itself  in  the 
cold  with  oil  of  vitriol  it  very  slowly  develops  a  purple  reaction,, 
but  more  quickly  when  warmed.  It  passes  through  an  interme- 
diate yellow  stage,  particularly  well  marked  in  the  reaction,  which 
is  obtained  without  the  employment  of  heat,  and  during  which 


the  matter  is  wholly  in  solution.  Then  flocks  separate  and  slowly 
become  purple. 

Two  quantations  of  phosphorus  were  made  :  No.  1  gave  0-045 
per  cent.,  and  No.  2  gave  0*051  per  cent.  Taking  the  mean  of 
these  two  results,  we  have  0  048  per  cent,  of  phosphorus.  Cal- 
culated as  myelin,  this  would  give  1  per  cent,  as  the  amount  of 
phosphorised  substance  left  in  the  phrenosin. 

At  this  stage  of  its  purification  the  phrenosin  was  subjected  to 
elementary  analysis. 

Elementary  Analysis  of  Phrenosin,  C^^^Hw^NOg. — Carbon,  hydrogen 
and  nitrogen  were  determined  simultaneously  by  the  vacuum 
method.  The  substance  was  burnt  with  oxide  of  copper  and  copper 
in  vacuo,  the  resulting  water  was  weighed,  and  the  gaseous  mixture 
of  carbonic  acid  and  nitrogen  was  analysed  and  estimated  volu- 

The  nitrogen  was  further  determined  by  the  methods  of  Liebig 
and  of  Dumas  as  modified  by  Thudichum  and  Wanklyn,  and 
by  the  proceeding  of  Will  and  Varrentrapp.  The  percentages 
obtained  in  these  analyses  are  compared  in  the  following  table  : 

By  combustion  in 

By  combustion  in  vacuo  ;  C  CO2  atmosphere;  By  combustion  with 

and  N  volumetrically ;  CO2  gas  volumetri-  soda-lime ;  Pt  salt. 
HoO  weighed,  wgd.     cally  estimated.  weighed. 

a.  h.  c.       d.       e.      f.       g.       h.       i.  k. 

C  67-71  67-89  67-37  68-56 

H  11-62  11-42  11-23 

N    2-15  2-13      2-07  2-29  2-18  2-34  1-768  1-690  1-715 

0  18-51  18-58  19-03 

100-00  100-00  100-00 

Consideration  of  the  Methods  of  Analysis. — The  quantation  of  the 
nitrogen  as  gas,  whether  it  has  been  obtained  by  combustion  in  a 
vacuum  or  by  combustion  under  atmospheric  pressure  in  an 
atmosphere  of  carbonic  anhydride,  always  gives  the  nitrogen  a. 
little  too  high  as  compared  to  theory,  whereas  the  estimation  of 
nitrogen  by  transformation  into  ammonia  always  gives  the  amount 
of  this  element  a  little  lower  than  is  required  by  theory.  These 
discrepancies  are  well  known  to  be  inherent  in  the  methods. 
They  are  less  significant  as  regards  the  analysis  of  bodies  which 
are  rich  in  nitrogen,  than  in  the  analysis  of  bodies  containing  only 
a  small  percentage  of  this  element.    In  the  particular  case  of 


phrenosin  they  are  so  great  as  to  make  it  at  first  sight  impossible 
to  derive  a  correct  empirical  formula  from  the  data  given  by  either 
mode  of  analysis.  But  the  mean  of  the  data  for  nitrogen  obtained 
by  the  three  different  modes  of  analysis  is  very  nearly  coincident 
with  the  sum  of  the  data  obtained  by  the  chemolytic  method. 
This  coincidence  is  probably  the  result  of  accident  only,  at  least 
there  is  at  present  no  explanation  derivable  from  the  most  search- 
ing scrutiny  of  either  of  the  methods  employed,  or  of  the  parti- 
cular manner  in  which  they  ha^^e  been  executed. 

In  the  vacuum  analysis  the  carbon  is  regularly  found  a  little 
too  loAv  j  yet  not  a  trace  of  carbon  is  left  unburned  in  the  tubes, 
as  was  specially  proved  ;  moreover,  the  combustion  tubes  with 
their  contents  were,  weighed,  before  and  after  combustion,  and 
"the  weights  of  the  sums  of  the  ])roducts  of  combustion,  as  calcu- 
lated from  their  volumes  in  the  case  of  carbon  and  nitrogen, 
showed  an  almost  mathematical  coincidence  with  the  respective 
losses  which  the  tubes  had  undergone. 

In  this  case  of  phrenosin  the  known  methods  of  elementary 
analysis  are  therefore  unavailing  to  lead  to  final  results ;  on  the 
contrary,  phrenosin  is  a  good  test  object  by  the  use  of  which  the 
particular  failings  as  well  as  strong  features  of  these  methods  can 
be  made  apparent.  Thus,  combustion,  according  to  Liebig,  of 
not  too  small  a  quantity  of  phrenosin  j'ields  the  best  carbon  esti- 
mate ;  combustion  in  vacuo  of  such  a  small  quantity  as  that  to 
which  the  method  is  necessarily  limited,  the  worst. 

The  very  same  methods  which  in  the  case  of  phrenosin  yield 
the  results  discussed  in  the  foregoing,  give,  when  applied  to  its 
decomposition-products,  results  which  are  in  much  greater  con- 
cordance with  the  requirements  of  theory.  This  unquestionable 
fact  shows  that  the  size  of  the  molecle,  and  the  proportions  in 
which  the  elements  contained  stand  to  each  other,  have  an  influ- 
ence on  the  result  of  the  process  of  elemcntar\^  analysis  ;  a  simple 
compound  of  fewer  atoms  gives  more  accurate  results  when  tested 
by  different  methods,  while  a  more  complicated  compound  with 
many  atoms,  when  tested  in  the  same  manner  by  different  methods, 
gives  much  less  accurate  results.  It  is  in  accordance  with  this 
that  the  elementary  analyses  of  the  more  com})licated  nitrogenised 
bodies,  such  as  kerasin  and  cerebrinic  acid,  present  even  greater 
difficulties  than  those  which  have  been  experienced  in  the  analysis 
of  phrenosin. 


1).  Chemolysis  of  Phrenosin  hy  Sulj^huric  Acid  in  Watery  Solution. 

Introduction. — In  my  earliest  chemolyses  with  barita,  hermeti- 
cally sealed  glass  tubes,  enclosed  in  iron  tubes,  were  employed. 
But  of  these  at  least  half  succumbed  to  the  internal  pressure,  and 
their  contents  were  lost.  I  therefore  procured  a  special  tube  of 
brass  lined  with  platinum.  This  worked  satisfactorily  for  the 
barita  chemolyses,  which  were  effected  in  a  short  time  ;  but  the 
sulphuric  acid  chemolyses  were  found  for  their  completion  to 
require  the  influence  of  a  temperature  of  at  least  130°  for  a  period 
varying  from  310  to  370  hours.  It  was  therefore  necessary  to 
multiply  the  tubes,  and  in  order  to  do  this  consistently  with 
practical  considerations  leaden  tubes  were  employed.  Such  tubes 
could  not  have  been  employed  in  the  barita  chemolysis,  as  barita. 
rapidly  and  energetically  attacks  lead.  But  dilute  sulphuric  acid 
has  but  a  slight  influence  on  metallic  lead,  and  the  small  quantity 
of  metal  which  is  dissolved  is  easily  removed  from  the  organic 
products  by  appropriate  means. 

The  Apparatus. — The  Leaden  Tubes. — The  Hot-Air  Stove. — The 
leaden  tubes  are  an  inch  in  calibre  ;  the  metal  is  an  eighth  of  an 
inch  thick  ;  each  tube  is  eighteen  inches  long.  One  end  of  the 
tube  is  closed  by  hammering  only  so  as  to  form  a  semi-globular 
end,  not  larger  in  diameter  than  the  tube  itself ;  it  is  tested  by 
water,  and  when  none  passes  it  is  soldered  over  on  the  outside. 
The  mixture  to  be  chemolysed  is  now  put  into  the  tube  by  means 
of  a  wide-tubed  funnel ;  the  upper  part  of  the  tube  is  heated  to 
dry  it  completely  and  rarefy  the  air. in  the  air-space,  which 
amounts  to  about  one-sixth  of  the  length  of  the  tube  ;  the  mouth 
of  the  tube  is  now  suddenly  compressed  in  a  vice  and  closed  ;  the 
edges  of  the  lead  are  filed  smooth,  moistened  with  zinc  chloride^ 
and  immediately  soldered,  or,  as  the  operation  is  technically 
termed,  '  burnt,'  with  the  oxyhydrogen  flame. 

The  hot-air  stove  is  made  of  copper,  and  consists  of  tivo  horizon- 
tal air  cushions,  between  which  special  room  for  six  of  the  leaden 
tubes  just  described  is  arranged  so  that  their  longest  axes  are 
lying  in  a  horizontal  position.  The  tubes  can  thus  be  kept  at  an 
equable  temperature,  which  can  be  read  by  the  thermometer,  the 
ball  of  which  is  in  the  central  air-space,  while  the  stem  projects 
over  the  top  of  the  stove.  The  stove  is  heated  by  aerated  gas- 


FreHminarij  Piuificatioa  from  Inorganic  Salts  of  the  Phrenosin  to 
he  Chemolijsed. — As  phrenosin  retains  inorganic  salts  with  great 
pertinacity,  it  must  be  subjected  to  a  process  for  the  removal  of 
these.  It  is  boiled  in  water  until  completely  disintegrated,  and 
the  boiled  mixture  is  pressed  through  a  cloth.  The  filtrate  is 
then  mixed  with  sulphuric  acid  sufficient  for  it  to  contain  1  per 
cent,  and  boiled  for  one  hour.  The  phrenosin  is  soon  curdled  out 
of  the  solution,  free  from  salt  but  partially  altered.  For  the  acid 
solution  after  treatment  with  barita  carbonate  is  found  to  contain 
some  chemolytic  sugar  (cerebrose)  besides  some  alkaloidal  matters, 
and  the  potassium,  sodium,  and  earthy  salts  which  it  is  the  object 
of  the  process  to  remove. 

Chemolysis  of  the  Purified  Substance. — Six  leaden  tubes,  prepared 
■as  above,  receive  each  about  30  g.  of  nitrogenised  substance 
purified  as  described,  and  353  cc.  of  dilute  sulphuric  acid  contain- 
ing 2  per  cent.  H^SO^.  The  tubes  are  then  closed  as  described, 
placed  in  the  hot-air  stove,  and  heated  to  130^  during  twenty- 
four  hours.  After  the  lapse  of  this  period  the  tubes  are  opened 
at  the  compressed  end  with  "a  chisel,  the  dilute  acid  is  removed 
and  filtered,  all  solid  matter  is  kept  in  the  tubes  cr  returned  to 
them  together  with  a  fresh  charge  of  acid ;  the  tubes  are  again 
closed  as  described,  and  heated  for  a  second  twenty-four  hours. 
This  treatment  is  repeated  as  long  as  the  acid  liquid  contains 
any  cerebrose,  and  the  chemolyses  are  deemed  complete  only 
when  the  last  charge  of  dilute  acid  is  found  on  proper  treat- 
ment and  concentration  to  be  free  from  cerebrose.  This  result 
is  in  most  cases  not  attained  in  less  than  fourteen  days,  and 
in  some  requires  from  sixteen  to  seventeen  days,  in  a  few  even 
twenty-four,  during  which  the  chemolysis  is  continued  day  and 

The  Acid  Filtrates. — These  are  boiled  w^ith  barium  carbonate, 
prepared  pure  by  precipitation  for  the  purpose.  The  neutral 
filtrates  are  evaporated  to  about  one-fifth  of  their  bulk  in  a  water- 
bath,  then  removed  into  a  distilling  apparatus  connected  with  an 
air-pump,  and  distilled  at  a  temperature  of  from  30'  to  40°  to  the 
consistency  of  a  syrup.  The  latter  is  put  aside  to  crystallise. 
Stellate  groups  of  crj'stals  soon  form,  and  the  entire  syrup 
gradually  solidifies  to  a  granular  mass  of  crystals.  These  are 
separated  partly  by  drawing  off  the  small  quantity  of  mother- 
liquor,  partly  by  agitating  them  with  water,  and  getting  rid  of 


the  mother-liquor  by  dilution  ;  for  the  crystals  are  but  slowly 
soluble  in  cold  water. 

From  the  mother-liquor  a  further  quantity  of  crystals  is  ob- 
tained by  addition  of  boiling  alcohol  to  the  hot  concentrated 
aqueous  solution  until  a  considerable  permanent  turbidity  is  pro- 
duced. When  the  mixture  is  alloAved  to  stand  in  the  cold  for 
one  day,  it  forms  a  considerable  amount  of  a  coloured  deposit, 
from  which  the  clear  supernatant  alcoholic  liquid  is  decanted. 
This  latter  solution  on  standing  for  some  weeks,  and  after  re- 
j^eated  additions  of  small  quantities  of  alcohol,  and  lastly  of  ether, 
deposits  a  crop  of  white  crystals  which  are  added  to  those 
obtained  in  the  first  operation. 

The  mother-liquors  are,  however,  always  considerable  in  amount, 
and  after  concentration  yield  an  uncrystallisable  syrup,  which 
amounts  to  about  the  same  weight  as  the  crystals  obtained  from 
it.  The  syrup  can  be  made  to  crystallise  a  third  time  after  the 
removal  of  some  traces  of  potassium  and  of  a  compound  am- 
monium base  by  platinic  chloride,  and  the  removal  of  all  traces 
of  the  reagent  by  hydrothion  and  silver  carbonate. 

c.  Cerebrose,  a  New  Crystallised  Sugar. 

The  Crystals. — Cerebrose  CgH^^O^. — The  crystals  obtained  as 
described  in  the  foregoing  are  dissolved  in  water,  and  the  solution 
is  evaporated  in  vacuo,  after  treatment  with  animal  charcoal.  A 
mass  of  crystals  is  again  obtained,  which  are  smaller  than  the 
first  ones,  but  perfectly  white  and  very  hard.  The  colourless 
mother-liquor  of  these  on  standing  over  .oil  of  vitriol  solidifies  to 
.a  hard  mass  of  crystals,  which  rise  much  over  the  level  of  the 
liquid  in  which  the}^  form.  The  crystals  are  not  large  enough 
for  crystallometric  treatment ;  seen  under  the  microscope  they 
seem  to  consist  of  rhombic  octahedra,  of  which  some  are  elongated 
to  prisms.  It  is  a  kind  of  sugar,  to  which  I  have  given  the  name 
•of  Cerebrose.  On  elementary  analysis  it  gives  analytical  data, 
leading  to  formula  C^H^gOc- 

Eeditcing  Power  of  Cerebrose  over  Cupro-Potassic  Tartrate. — Cere- 
brose reduces  Fehling's  solution  readily  on  heating,  and  the 
precipitated  suboxide  of  copper  is  mostly  of  a  dark-red  colour. 
■0-2622  g.  cerebrose  dried  in  the  water-bath  were  dissolved  in 
water,  and  the  solution  made  to  fill  the  space  of  50  cc.  This 
solution  therefore  contained  0-5245  per  cent,  of  cerebrose.  It 


was  employed  to  reduce  a  Fehling's  solution  of  which  5  cc.  re- 
quired 0*025  g.  of  glucose  for  decoloration.  Five  cc.  of  the 
Fehling's  solution  required  5-6  cc.  of  the  cerebrose  solution  for 
decoloration,  equal  to  0-0294  g.  cerebrose.  A  certain  quantity  of 
cupro-potassic  tartrate,  therefore,  which  requires  five  parts  of 
glucose  for  complete  reduction,  requires  about  six  parts  of  cere- 
brose for  reduction. 

Polarising  Poicer  of  Sohttion  of  Cerebrose. — Some  cerebrose  was- 
dried  in  the  air-bath  at  90°,  and  in  vacuo  till  it  remained  constant 
in  weight.  Of  this  2-6315  g.  were  dissolved  in  water  with  the 
aid  of  a  gentle  heat,  and  made  to  fill  a  space  of  20  cc.  The  solu- 
tion was  treated  with  animal  charcoal  to  remove  a  slight  turbidity. 
Its  strength  remained  at  13-16  per  cent.  This  in  a  tube  of  100  mm. 
length  rotated  the  ray  of  polarised  light  at  25°  T=  +10°  40' ;  but 
after  twenty-four  hours'  standing  the  same  tube  at  T  11°  rotated 
only  +  9°  24';  after  a  second  twenty-four  hours,  at  T  12°=  -|-  9°  18'. 
The  solution  was  then  diluted  with  an  equal  bulk  of  water,  and 
its  rotation,  measured  in  a  tube  twice  the  length  of  the  former^ 
was  found  to  be  +  9°  24'  at  9°  T  to  9°  32'  at  8°  T.  These  data, 
by  means  of  the  usual  calculation,  lead  to  the  specific  or  limited 
rotation  for  cerebrose  of  +  70°  40'.  It  will  be  observed  that  im- 
mediately after  solution  the  rotation  is  a  little  higher  than 
twenty-four  hours  after  solution,  when  it  becomes  constant.  But 
this  increase  of  the  rotation  is  very  slight  compared  with  the  in- 
crease which  dextroglucose  exhibits  immediately  after  solution, 
and  which,  from  the  fact  of  its  being  about  as  much  again  as  the 
constant  rotation,  is  termed  the  birotation  of  glucose. 

The  molecular  formula  of  cerebrose  is  assumed  in  the  foregoing 
to  be  C^3HjoO,3.  Cerebrose  resembles  sugar  of  milk  by  its  feebly 
sweet  taste  and  the  great  hardness  of  its  crystals. 

Other  Properties  if  Cerebrose. — The  crystallised  cerebrose  is  never 
obtained  without  the  amorphous  modification  being  formed  at  the 
same  time.  To  judge  from  comparison  of  bulks,  at  least  half  the 
cerebrose  obtained  during  the  chemolytic  operations  on  the  nitro- 
genised  principles  passes  into  the  amor2)hous  state,  and  cannot  be 
made  to  crystallise  entirely  even  within  the  period  of  a  year. 
Crystalline  particles  of  pure  cerebrose  immersed  in  the  syrup  in- 
crease in  size,  and  form  ramifications  ;  but  their  growth  ceases 
after  a  time,,  and  the  syrup  thereafter  remains  unchanged.  The 
difficulty  of  separating  the  two  modifications  is  increased  by  the 


occasional  appearance  of  a  third  form  of  product  of  the  chemolytic 
metamorphoses  of  the  amylonide  radicle  of  the  nitrogenised  bodies 
which  I  shall  presently  describe. 

Cerebrose  is  precipitated  from  its  watery  solution  by  basic  lead 
acetate  or  by  a  mixture  of  neutral  lead  acetate  and  ammonia ;  the 
mother-liquor  of  this  precipitate  no  longer  reduces  potassio-cupric 
tartrate,  from  which  it  may  be  inferred  that  the  precipitation  of 
the  cerebrose  is  complete.  The  lead  compound  of  cerebrose  after 
decomposition  by  hydrothion  yields  the  cerebrose  in  the  free  state. 
In  its  affinity  for  lead  oxide  cerebrose  resembles  inosite,  the  sugar 
naturally  contained  in  the  brain,  and  obtained  as  an  educt  from 
the  water  extracts ;  but  it  is  easily  distinguished  from  inosite  by 
its  power  over  polarised  light  and  potassio-cupric  tartrate,  reactions 
which  inosite  does  not  possess. 

The  Uncrystallised  Cerebrose. — The  uncrystallised  cerebrose  ob- 
tained from  the  nitrogenised  substances  by  the  process  of 
chemolysis  above  described  may  be  a  product  from  the  crj^^stal- 
lised  j  at  least,  when  the  watery  solution  of  the  sugar  is  evapo- 
rated in  the  open  air  on  the  water-bath  no  crystallised  sugar  is 
ever  obtained,  but,  as  previous  experience  and  renewed  experi- 
ment have  shown,  only  uncrystallisable  cerebrose.  Only  w^hen 
the  solution  is  evaporated  in  a  vacuum  ensuring  the  absence  of 
air,  and  at  a  temperature  never  rising  above  that  of  the  animal 
body,  37°,  is  crystallisable  cerebrose  obtained — accompanied, 
however,  always  by  a  considerable  proportion  of  uncrystallisable 
cerebrose,  amounting  in  weight  to  about  that  of  the  crystallisable 
cerebrose.  There  is,  therefore,  room  for  an  inquiry  into  the 
causes  of  these  phenomena. 

The  chemical  constitution  of  cerebrose  now  arises  as  a  subject 
of  inquiry  of  interest  and  importance.  Not  only  is  there  a  new 
isomer  added  to  the  long  list  of  saccharoid  substances  already 
known,  but,  what  is  of  much  greater  value,  a  new  key  is  found  to 
the  knowledge  of  the  constitution  of  some  of  the  organoplastic 
substances.  This  will  enable  us  to  obtain  a  full  knowledge  of  the 
constitution  of  the  nitrogenised  substances  of  the  brain  much 
quicker  than  would  be  the  case  without  such  theoretical  aid ;  for 
the  number  and  nature  of  the  problems  are  now  at  once  limited 
and  defined,  as  we  shall  see  presently  by  the  aid  of  further  new 

Cerebrosic  Acid,   C^fl-^Q('H.2)0^^. — This  new  acid,  obtained  by 



means  of  the  chemolytic  process  from  phrenosin,  has  the  compo- 
sition of  a  carbohydrate,  and  is  probably  isomeric  with  cerebrose. 
It  has  not -yet  been  examined  any  closer  in  the  free  state,  but  the 
examination  of  its  barium  salt  leads  to  the  inference  that  it  is  a 
dibasic  acid  of  the  formula  C,3Hj.20j3.  It  is  obtained  as  folloAvs  : 
25  g.  of  pure  phrenosin  are  suspended  in  300  cc.  of  water,  and  to 
the  mixture  2  cc.  of  oil  of  vitriol  are  added.  The  whole  is  en- 
closed in  the  platinum  chemolyser,  and  heated  to  120°  during 
seven  days  without  interruption.  The  acid  liquid  from  the 
chemolyser  is  now  filtered  and  treated  with  barium  carbonate  at 
the  boiling  heat.  The  filtrate  (which  in  the  chemolyses  of 
phrenosin,  where  the  dilute  sulphuric  acid  is  renewed  every 
twenty-four  hours,  mainly  contains  cerebrose)  has  no  reducing 
effect  at  all  upon  potassio-cupric  tartrate,  but  contains  a  con- 
siderable amount  of  barium  in  solution.  When  evaporated  quickly 
to  dryness,  it  leaves  as  residue  a  hard  amorphous  barium  salt ; 
but  when  dissolved  in  a  little  spirit  and  allowed  to  stand,  it 
slowly  sets  into  a  mass  of  indistinct  crystals.  These  are  freed 
from  mother-liquor  by  pressure  between  folds  of  bibulous  paper 
dried  at  100°  C,  and  analysed  with  the  following  result  : 

Synopsis  of  Analyses  of  Barium  Cerebrosate. 



-^At  wts. 

















These  data  lead  to  a  formula  BaCgHj^O^j,  corresponding  to  an 
acid  of  the  composition  of  cerebrose  in  which  two  atoms  of 
hydrogen  are  replaced  by  an  atom  of  barium.  It  reminds  of 
glucic  acid,  which  is  also  dibasic.  Glucic  acid  is  prone  to  form 
bodies  like  the  caramels,  and  the  presence  of  a  small  proportion 
of  one  or  other  of  these  bodies  seems  to  be  the  cause  of  an  excess 
of  carbon  over  the  theoretical  amount  which  is  met  with  in  the 
analysis  of  its  salts.  A  similar  feature  is  observed  upon  the 
cerebrosate  of  barium,  which  also  exhibits  a  slight  excess  of 
carbon  and  a  deficiency  of  hydrogen  and  oxygen.  The  salt 
is  free  from  nitrogen,  and  does  not  contain  sulphuric  acid  in 
organic  combination.  When  distilled  with  phosphoric  anhydride 
it  does  not  give  out  the  odour  of  acrolein,  but  a  smell  resembling 


burnt  sugar.  With  oil  of  vitriol  alone  it  gives  no  purple  reaction. 
Mixed  with  sphingosin  and  oil  of  vitriol  it  gives  a  brilliant  purple 
reaction,  equal  in  tint  to  that  produced  by  the  aid  of  cerebrose. 
But  even  its  concentrated  solution  has  no  influence  on  the  alkaline 
copper  solution. 

Transformation  of  Baiium  Salt  of  Cerebrosic  Acid  into  Zinc  Salt. — 
The  barium  salt  is  decomposed  with  dilute  sulphuric  acid,  and  the 
solution  extracted  with  ether.  The  ether,  on  distillation,  leaves 
an  acid  which  is  converted  into  zinc  salt :  the  latter  is  crystallised 
and  analysed.  The  air-dried  salt  loses  9-8  per  cent,  of  water  at 
100°  C.  The  remaining  dry  salt  is  burnt,  and  the  zinc  estimated, 
from  the  remaining  oxide,  to  amount  to  28  per  cent,  of  air-dried 
salt.  From  these  data  it  seems  that  the  zinc  salt  is  entirely 
different  from  any  of  the  known  lactates.  The  barium  salt, 
though  different  in  appearance  from  lactate,  is  isomeric  with  it. 

Attempt  to  produce  Cerebrosic  Acid  from  Free  Cerebrose. — A  con- 
sideration of  the  conditions  under  which  this  acid  has  been  pro- 
duced from  phrenosin  suggests  that  it  might  have  been  formed  by 
the  prolonged  action  of  heat  and  acid  upon  cerebrose  formed 
during  the  earlier  stages  of  the  reaction.  In  the  experiments 
in  which  cerebrose  was  obtained,  the  influence  of  acid  and  heat 
upon  the  phrenosin  was  interrupted  every  twenty-four  hours,  and 
the  acid  was  renewed.  In  the  experiment,  however,  which  yielded 
cerebrosic  acid,  the  action  of  acid  and  heat  had  been  continuous 
during  seven  days  and  nights.  It  was  therefore  necessary  to  in- 
vestigate whether  cerebrose  already  formed  could  be  transformed 
into  cerebrosic  acid  under  the  circumstances  related,  or  whether  it 
could  be  so  transformed  only  in  the  nascent  state,  and  what  were 
the  other  conditions  of  this  transformation. 

About  2  g.  of  amorphous  cerebrose  were  heated  with  water 
containing  1  per  cent,  of  oil  of  vitriol,  to  120°  during  nine  days. 
There  were  formed,  firstly,  a  considerable  amount  of  caramel ; 
and  secondly,  a  quantity  of  an  acid  corresponding,  as  regards  its 
properties  and  those  of  its  salts,  to  cerebrosic  acid.  But  a  large 
proportion  of  the  cerebrose  remained  unchanged.  The  caramel 
was,  like  the  acid,  soluble  in  ether. 

Caramel  obtained  in  the  Chemolysis  of  Phrenosin  in  which  Cere- 
brosic Acid  was  formed. — Of  this  caramel  2-1  g.  were  obtained.  It 
was  very  soluble  in  ether,  and  somewhat  soluble  in  alkaline  water, 
but  insoluble  in  alcohol  and  in  acidulated  water.    It  was  of  a  deep 



brown  colour,  like  all  the  bodies  of  this  class.  From  a  considera- 
tion of  the  several  forms  of  caramel  which  are  obtained  from  the 
several  principles  of  the  nitrogenised  group,  as  will  be  shown  in 
another  chapter,  it  becomes  probable  that  the  caramel  here  formed 
was,  in  part  at  least,  the  caramel  of  psychosin.  This  supposi- 
tion is  strengthened  by  the  consideration  of  the  relative  quantities 
of  the  several  products  of  the  chemolysis  of  phrenosin.  The  25  g. 
of  this  body  employed  in  the  experiment  related  above  gave  4-6  g. 
of  cerebrosic  acid.  The  theoretical  amount  which  could  have 
been  obtained  in  the  best  case  would  have  been  6*2  g.  Con- 
sequently 1  -6  g.  of  the  amylonide  radicle  must  have  been  trans- 
formed into  bodies  other  than  cerebrose  and  cerebrosic  acid.  The 
2-1  g.  of  caramel  found  in  the  present  experiment  could  not 
have  been  caramel  of  cerebrose  simply,  as  the  atomic  weight  of 
that  body  is  much  smaller  than  that  of  cerebrose.  But  it  could 
have  been,  or  contained,  some  caramel  of  psychosin,  the  atomic 
weight  of  which  is  more  than  twice  that  of  cerebrose.  The  other 
products  insoluble  in  water  were,  sphingosin,  which  as  sulphate 
weighed  2-5  g.,  corresponding  to  about  2*13  g.  free  sphingosin, 
and  an  unascertained  quantity  of  another  alkaloid,  probably 
psychosin,  which  remained  in  the  alcohol  from  which  the  sphin- 
gosin was  precipitated  by  sulphuric  acid.  The  amount  of  free 
fatty  acid  obtained  was  9*4  g.  This  was  almost  entirely 
neurostearic  acid,  and  its  quantity  came  very  near  to  that 
required  by  theory,  which  is  9-9  g.  The  total  of  weighed 
products  of  chemolysis  amounted  to  18*2  g.  ;  the  psychosin  or 
second  base  was  not  weighed,  and  allowing  for  this,  certainly  a 
few  grammes,  and  much  for  loss  in  the  many  difficult  manipula- 
tions, the  fate  of  the  phrenosin  originally  employed  is  pretty  well 
accounted  for. 

In  almost  all  chemolyses  of  nitrogenised  principles  by  acids  or 
alkalies  in  watery  or  sj)irituous  solution  there  has  been  formed 
cerebrose,  cerebrosic  acid,  psychosin,  caramel  of  psychosin,  sphin- 
gosin, and  neurostearic  acid  or  its  ether.  When  the  cerebrose 
solution  was  freed  from  sulphuric  acid,  after  chemolysis  with  an 
acid,  it  always  retained  some  baryta,  which  had  to  be  removed 
by  precipitation  with  sulphuric  acid.  It  is  therefore  possible 
that  the  cerebrose  is  always  accompanied  by  some  cerebrosic 
acid ;  attempts  should  be  made  to  extract  this  by  ether  before 
evaporating  the  cerebrose  solution  to  a  small  bulk,  as  otherwise 


the  acid  may  contribute  to  transform  the  cerebrose  into  the  un- 
crystallisable  modification. 

cl.  Sphingosin,  a  neiv  Alkaloid,  as  Sulphate,  and  Fatty  Acids. 

The  solid  products  from  the  chemolytic  tubes  are  united,  edul- 
corated with  water,  dissolved  in  hot  spirit,  decolorised  with  animal 
charcoal,  crystallised  and  dried.  In  a  state  of  fine  powder  they  are 
extracted  with  pure  ether  in  the  cold.  The  fatty  acids  dissolve, 
while  a  body  remains  insoluble,  which  is  of  an  alkaloidal  nature, 
and  to  which,  in  commemoration  of  the  many  enigmas  which  it 
presented  to  the  inquirer,  I  have  given  the  name  of  Sphingosin. 

The  part  insoluble  in  ether  is  again  treated  with  alcohol,  but 
the  substance,  previously  freely  soluble  in  spirit,  now  becomes 
more  and  more  insoluble,  and  at  last  fuses  and  becomes  quite  in- 
soluble even  in  absolute  alcohol.  It  is  now  easily  soluble  in 
benzol  in  the  cold.  Addition  of  any  acid  to  the  hot  alcohol  restores 
the  solubility  of  the  body,  and  on  cooling  the  body  crystallises 
again.  This  bearing  leaves  little  doubt  that  the  body  is  a  salt- 
like combination  of  an  organic  base  with  the  acid  employed, 
soluble  in  alcohol  in  the  presence  of  an  excess  of  acid,  insoluble 
in  the  absence  of  such  excess. 

Removal  of  the  Sidplmric  Acid  by  Caustic  Allccdi, — The  salt  is 
freed  from  spirit  by  water,  and  then  while  diffused  in  water  is 
treated  with  caustic  soda  ley  and  heated.  The  flaky  body  at  once 
transforms  into  oily  drops,  which  rise  to  the  surface  of  the  liquid. 
On  cooling  this  oily  liquid  does  not  set  like  a  fat,  but  becomes 
again  opaque,  and  distributed  in  flakes  through  the  fluid.  The 
oil  is,  however,  easily  soluble  in  pure  ether  (in  which  the  salt  had 
been  previously  insoluble),  and  is  extracted  by  this  solvent.  The 
solution  is  filtered,  the  ether  distilled  off",  the  residue  dissolved  in 
absolute  alcohol  and  decolorised  by  animal  charcoal.  Minute 
quantities  of  impurities,  probably  of  soda-soap,  which  deposit 
from  the  ether  solution  and  from  this  last  alcoholic  solution  on 
standing,  are  removed  by  filtration.  This  alcoholic  solution  of 
the  free  base,  which  is  alkaline  to  test  paper,  gives  the  following 
reactions.  Oil  of  vitriol  in  absolute  alcohol  gives  an  immediate 
white  precipitate  of  a  sulphate.  Hydrochloric  acid  gives  a  pre- 
cipitate of  a  hydrochlorate ;  both  precipitates  are  soluble  in  cold 
alcohol  with  the  aid  of  excess  of  acid.  An  alcoholic  solution  of 
cadmic  chloride  gives  a  precipitate  soluble  in  excess  of  absolute 


alcohol.  Mercuric  chloride  gives  a  flaky  precipitate  which  settles 
easily.  Water  causes  a  gelatinous  precipitate  in  the  alcoholic 
solution.  Ether  or  alcohol  solution  leave  the  base  in  a  crystalline 
state  on  evaporation.  It  is  very  slightly  if  at  all  soluble  in 
water,  even  on  boiling.  When  dry  it  gives  no  purple  colour  with 
oil  of  vitriol  alone  on  gentle  warming,  but  on  addition  of  sugar 
gives  immediately  a  deep  purple  colour.  The  full  significance  of 
this  reaction  will  be  discussed  lower  down. 

Sphingosin  Sulphafe.-^A  solution  of  the  free  base  in  cold  absolute 
alcohol  is  precipitated  with  a  freshly  made  solution  of  oil  of  vitriol 
in  absolute  alcohol  with  the  precaution  of  keeping  the  alkaloid  in 
excess.  The  white  crystalline  precipitate  is  washed  with  absolute 
alcohol,  pressed,  and  dried  in  vacuo  over  sulphuric  acid. 

Elementary  analysis  leads  to  the  formula  for  sphingosin  sul- 
phate of  2(CjK.H35N02)  +  H2SO^,  of  which  the  theory  is  compared 
with  the  experimental  data  in  the  following  table  : 

Theory  of 

f  ^ 

Atoms.  Found. 

^  ,   Percents.  Percents. 

34  C                408  60-11  60-85 

72  H                72  10-78  10-70 

2  N                 28  4-19  4-14 

4  0                 64  —  — 


Sjjhingosin  Hydrochlomte. — On  adding  to  a  concentrated  solution 
of  sphingosin  in  absolute  alcohol  or  in  spirit  some  hydrochloric 
acid,  a  turbidity  or  precipitate  is  at  once  produced.  If  the  mixture 
is  warmed  and  allowed  to  cool  gradually  under  a  dryer  over  oil 
of  vitriol,  masses  of  spear-shaped  crystals  form  in  the  fluid  which 
can  be  removed  as  a  felted  mass.  The  crystals  under  the  micro- 
scope appear  as  uniform  needles  with  pointed  pyramidal  ends. 
The  analytical  data  concerning  this  salt  show  that  its  formula  is 
C17H05NO2  +  HCI.  It  does  not  easily  form  double  salts  with 
metallic  chlorides. 

The  purification  of  sphingosin  is  based  upon  its  precipitation 
from  absolute  alcohol  by  sulphuric  acid  and  the  decomposition  of 
the  sulphate  in  water  by  caustic  alkali ;  the  oily  mass  when  freed 


from  all  alkaline  liquid  can  be  boiled  with  water,  and  thus  freed 
entirely  from  alkali.  In  this  way  two  impurities  which  may 
accompany  sphingosin  in  small  quantities  are  entirely  removed ; 
one  a  body  soluble  in  ether,  and  which  will  be  described  here- 
after ;  another  an  acid  of  which  also  a  small  quantity  escapes  the 
first  extraction  by  ether,  in  which  the  bulk  of  the  acid  formed  in 
the  chemolysis  is  separated.  Both  remain  in  the  absolute  alcohol 
from  which  the  sphingosin  is  precipitated  by  sulphuric  acid.  But 
they  are  less  soluble  in  watery  alcohol  than  the  sphingosin,  and 
therefore  are  precipitated  by  water  or  watery  reagents  together 
with  the  sphingosin. 

Consideration  of  the  General  Chemical  Function  of  Sphingosin. — The 
consideration  of  the  molecular  formula  of  sphingosin  might  at 
first  sight  lead  to  the  hypothesis  that  it  contained  a  fatty  acid 
radicle  of  the  Qj^on^^  series,  and  that  in  this  an  atom  of  hydrogen 
was  replaced  by  the  amide  group  NH^,  as  expressed  by  the  formula 
Ci^H33(NH2)02.  Sphingosin  also  behaves  like  an  amido-acid  in 
this,  that  on  the  one  hand  it  combines  with  bases  such  as  potash, 
or  on  the  other  unites  with  acids  such  as  sulphuric  and  hydro- 
chloric. However,  its  qualities  as  an  acid  are  the  least  apparent, 
and  so  limited  that  they  subsist  in  any  degree  only  in  the  absence 
of  water.  In  the  presence  of  water  the  potash  compound  is  not 
formed  at  all ;  the  barium  compound  is  formed  in  the  presence 
of  water  and  excess  of-  barium  salt,  but  decomposes  during  every 
treatment  for  its  purification,  even  by  resolution  in  strong  spirit. 
The  salts  of  sphingosin  with  acids,  however^  are  very  firm  com- 
pounds ;  they  crystallise,  do  not  dissociate  in  solvents,  and  in  the 
dry  state  admit  of  convenient  manipulation.  By  its  greater 
affinity  for  acids,  sphingosin  indeed  differs  from  the  amido-acids 
and  resembles  more  the  alkaloids.  It  is  precipitated  by  most 
of  the  specific  reagents  which  combine  with  alkaloids,  and  there- 
fore on  the  whole  evidence  it  must  be  admitted  that  sphingosin 
is  an  alkaloid. 

Neutral,  Acid,  and  Basic  Salts  ;  Bearing  of  the  Sidphate. — When 
sphingosin  sulphate  is  treated  with  dry  neutral  ether,  it  remains 
undissolved.  When  the  mixture  is  acidified  with  sulphuric  acid, 
the  sulphate  dissolves  completely.  When  to  the  solution  some 
alkali  is  cautiously  added,  the  neutral  sulphate  is  again  precipi- 
tated in  flocks.  AVhen  neutral  sphingosin  sulphate  which  has 
been  dried  completely  is  digested  in  the  cold  with  aqueous 


ammonia,  sulphuric  acid  is  dissolved,  and  appears  in  the  filtrate. 
But  it  is  not  ^practicable  to  remove  all  the  sulphuric  acid  from  the 
sphingosin  by  this  treatment;  even  after  many  days'  washing 
the  alkaloid  retains  some  sulphuric  acid.  This  can  only  be  re- 
moved by  warming  the  compound  with  caustic  ley,  and  extracting 
the  free  alkaloid  with  ether. 

It  follows  from  the  foregoing  that  sphingosin  forms  neutral  and 
acid,  and  perhaps  basic,  salts. 

Bearing  of  the  Hydrochlorate. — The  hydrochlorate  of  sphingosin 
cr3^stallises  from  water  or  alcohol  in  long  spear-shaped  crystals. 
It  is  much  more  soluble  in  hot  water  than  in  cold  ;  it  is  deposited 
from  a  solution  in  water  which  also  contains  psychosin  almost 
entirel}^  if  the  solution  is  cooled  to  and  filtered  at  the  temperature 
of  melting  ice.  A  little  psychosin,  however,  easily  remains  with 
the  sjDhingosin,  so  that  in  analyses  of  the  latter  the  carbon  is 
sometimes  found  a  fraction  of  a  per  cent,  too  high.  The  admix- 
ture is  recognised  by  the  purple  test  with  sulphuric  acid,  and  is 
removed  by  recrystallisation  of  the  hydrochlorate ;  or  in  case  of 
the  sulphate,  by  transformation  into  the  free  base,  and  repre- 
cipitation  from  absolute  alcohol  by  sulphuric  acid.  The  psychosin 
salts  of  both  acids  are  the  more  soluble  ones. 

Sphingosin  uith  Fotash. — When  the  solution  of  free  sphingosin, 
prepared  from  the  pure  sulphate  in  ether,  is  dried  by  being 
allowed  to  stand  over  solid  caustic  potash,  a  dense  but  trans- 
lucent deposit  in  the  shape  of  flakes  and  crusts,  covering  the  sides 
of  the  vessel  and  the  masses  of  potash,  is  gradually  formed.  This 
is  a  compound  of  sphingosin  with  potash,  which  is  little  soluble 
in  the  anhydrous  ether.  It  has  not  yet  been  separated  from  the 
excess  of  potash.  The  ether  retains  a  certain  portion  of  this 
compound  in  solution,  and  leaves  it  as  a  hard,  dense,  colourless 
deposit  on  distillation.  A  preliminary  analysis  of  this  residue 
gave  61"0-1:  per  cent,  carbon,  9-96  per  cent,  hj^drogen,  4-52  per 
cent,  nitrogen,  and  6'53  per  cent,  potassium.  From  this  it  is 
evident  that  this  residue  is  a  mixture  of  a  compound  formed  of 
sphingosin  and  potassium  or  potash,  with  free  sphingosin.  The 
potassium  compound  Cj-Hg^vNOo  requires  12-1  per  cent,  of 
potassium.  The  mixture  therefore  contains  a  little  more  than 
half  its  weight  of  the  potassium  compound. 

Sejmraiion  of  Psychosin  from  Sphingosin.  — This  may  be  effected 
in  alcoholic  or  watery  solution.  The  mixed  alkaloids  are  dissolved 


in  absolute  alcohol,  and  a  very  dilute  solution  of  oil  of  vitriol  in 
absolute  alcohol  is  added  so  as  to  precipitate  all  sphingosin. 
From  the  filtered  alcoholic  mother-liquor  all  alcohol  is  removed, 
first  by  distillation,  afterwards  by  evaporation  with  water.  The 
residue  is  warmed  with  some  caustic  potash,  and  the  ley  which 
has  taken  up  any  sulphuric  acid  is  decanted.  The  washed  residue 
is  boiled  with  hydrochloric  acid,  in  which  it  dissolves  readily. 
The  solution  is  filtered  hot,  and  concentrated  to  a  suitable  bulk. 
It  contains  all  the  psychosin,  and  if  the  precipitation  of  sphingosin 
by  sulphuric  acid  had  been  incomplete,  or  an  excess  of  the  acid 
had  been  added  so  as  to  redissolve  some  sphingosin  as  acid  sul- 
phate, this  base  also  occurs  in  the  hydrochlorate.  The  solution, 
on  being  cooled  to  0°  C,  deposits  sphingosin  hydrochlorate  in 
colourless  crystals,  which  may  be,  filtered  off  in  the  cold,  but 
cannot  be  washed  from  excess  of  psychosin  by  water,  as  they 
swell  and  make  filtration  impossible. 

Fatty  Acids  and  Matters  soluble  in  Ether,  being  Products  of  the 
Chemohjsis  which  yields  SjMngosin. — The  ether  solution  of  the 
chemolytic  products  obtained  as  described  above,  p.  149,  is  con- 
centrated, and  yields  several  deposits  of  fatty  matters  at  several 
stages.  The  first  deposit  after  recrystallisation  from  spirit 
resembles  neurostearic  acid  in  appearance.  It  begins  to  fuse 
at  73°,  but  does  not  wholly  fuse  till  the  temperature  reaches 
81°.  The  body  is  therefore  probably  neurostearic  acid,  mixed 
with  a  small  quantity  of  acid  of  lower  fusing-point.  It  is  con- 
verted into  barium  salt ;  this  is  extracted  with  hot  spirit,  and  the 
fatty  acid  is  again  extracted  from  the  barium  salt  by  tartaric  acid 
and  ether.  The  free  acid  now  fuses  at  80°  and  sets  at  79°;  it  has 
therefore  lost  some  of  the  fatty  acid  melting  at  a  lower  tem- 

The  later  deposits  from  ether  and  all  the  acids  most  soluble  in 
ether  are  converted  into  barium  salts  and  exhausted  with  boiling 
alcohol.  There  remains  insoluble  in  spirit  a  barium  salt,  which 
by  treatment  with  tartaric  acid  and  ether  gives  free  fatty  acid 
which  fuses  below  50°  C,  and  therefore  diff'ers  greatly  from  the 
acid  first  deposited  from  the  ether  solution. 

The  alcoholic  extracts  of  the  barium  salts  on  cooling  deposit  a 
solid  compound,  and  retain  in  solution  a  compound  which,  after 
evaporation  of  all  alcohol,  is  semi-solid  on  being  heated  with  water, 
and  dissolves  entirely  in  ether. 


We  therefore  obtain  four  principal  bodies  by  these  operations 
on  the  chemolysed  matters  soluble  in  ether.  Two  form  barium 
salts  insoluble  in  boiling  spirit,  and  are — the  first,  mainly  neuro- 
stearic  acid,  CigH3Q02 ;  the  other,  an  acid  of  lower  fusing-point, 
not  yet  studied  any  further.  Of  the  bodies  soluble  in  hot  spirit, 
one  is  soluble  in  ether.  The  significance  of  all  these  bodies  will 
be  made  clear  when  we  come  to  consider  the  chemical  constitu- 
tion of  the  non-phosphorised  group  of  nitrogenised  substances. 
Each  of  these  acids,  which  by  their  number  no  less  than  their 
properties  are  remarkable,  will  then  find  a  place  in  a  natural 
educt,  and  by  another  process  in  a  systematic  classification. 

e.  FsijcJiosin,  its  Properties  and  Metamorphoses. 

This  alkaloid  was  first  obtained  from  the  nonphosphorised 
group  of  nitrogenised  bodies  by  chemolysis  with  caustic  barita. 
The  mere  analysis  of  this  body  led  to  an  empirical  formula  of 
CggH^gNOg,  which  was  uncontrolled  by  combinations.  The  free 
body  had,  however,  crystallised  from  alcohol.  To  fill  up  this  void 
I  produced  some  combinations  with  hydrochloric  acid  and  with 
platinic  chloride,  but  the  products  had  the  peculiarity  of  some  of 
the  phosphorised  bodies,  namely  of  dissociating  in  the  presence 
and  under  the  influence  of  small  quantities  of  water.  The  hypo- 
thetical salt  would  have  contained  24*01  per  cent,  of  platinum, 
whereas  the  actual  salt  contained  only  21*05  j^er  cent.  But  the 
carbon  of  the  organic  molecle  decreased  slightly  in  relation  to  the 
nitrogen,  and  this  led  me  to  again  analyse  a  further  purified 
specimen  of  psychosin,  obtained  by  the  chemolysis  of  phrenosin. 

The  jjsychosin  was  dissolved  in  hydrochloric  acid  and  water, 
and  the  solution  made  perfectly  bright  and  colourless.  Tlie 
alkaloid  was  then  precipitated  by  ammonia,  washed  perfectly, 
dried  in  vacuo,  and  analysed. 

Summary  of  Analyses  of  Psychosin. 

Eirst  Analyses  (1876).  Later  Analyses  (1878). 

Percents.  Percents.  -r-by  At.  Wgts.     -r-l3yN  =  l. 

C  61-86  61-32  5-11  23-53 

H  10-09  10-09  1009  46-46 

N  2-88  3-04            -21716  1-00 

O  25-17  25-55  1-597  7*35 

Psychosin  Sul])hate. — Psychosin  is  soluble  in  very  dilute  sulphuric 
acid  on  boiling,  but  is  deposited  on  cooling.    The  mother-liquor 


of  the  deposit  after  twenty-four  hours  retains  only  a  small  amount 
of  the  salt  in  solution,  so  that  ammonia,  which  if  not  added  in 
excess  precipitates  psychosin  from  its  solution  in  water  and  hydro- 
chloric acid,  hardly  causes  any  precipitate.  But  phosphomolybdic 
acid  causes  a  more  appreciable  precipitate. 

Psychosin  Hyrochlorate. — When  to  a  sohition  of  neutral  psychosin 
hydrochlorate  in  water  an  excess  of  strong  hydrochloric  acid  is 
added,  a  bulky  gelatinous  precipitate,  much  resembling  hydrate 
of  alumina,  is  produced.  The  salt  is  so  completely  removed  from 
the  solution  that  the  latter,  after  filtration,  gives  no  precipitate 
with  phosphomolybdic  acid. 

When  a  solution  of  psychosin  hydrochlorate  is  kept  on  a 
dialyser  of  parchment-paper  floating  on  distilled  water  for  eighteen 
hours,  some  psychosin  as  well  as  some  hydrochloric  acid  pass  into 
the  water.  The  amount  which  passes  is  very  small,  and  no 
psychosin  is  deposited  on  the  dialyser.  Psychosin  is  therefore  a 
strong  base,  but  at  the  same  time  it  exercises  its  functions  as  a 
colloid,  such  as  it  becomes  in  the  presence  of  water  and  absence 
of  acids. 

Psychosin  precipitated  from  its  hydrochloric  solution  by  am- 
monia and  well  washed,  when  allowed  to  remain  in  contact  with 
pure  water  during  several  days,  becomes  hydrated,  and  swells  up 
to  a  voluminous  gelatinous  mass.  This  paste  retains  water  with 
great  force,  and  is  most  difficult  to  dry  in  vacuo  over  sulphuric 
acid.  Heat  causes  it  to  become  brown  at  once ;  even  in  the 
vacuum  it  assumes  colour. 

Psychosin  and  Ammonia. — Psychosin  dissolves  readily  in  con- 
centrated ammonia-water  on  boiling,  and  is  deposited  again  on 
cooling,  and  standing.  The  hot  ammonia  solution  gives  a  preci- 
pitate with  barium  chloride,  which  after  isolation  is  soluble  in 
boiling  alcohol  and  deposited  on  cooling.  This  compound  loses 
barium  by  all  attempts  at  recrystallisation. 

Chemolysis  of  Psychosin  by  Dilute  Sulphitric  Acid. — Psychosin  is 
enclosed  in  the  platinum  chemolyser  with  a  sufficiency  of  sulphuric 
acid  of  2  per  cent,  strength,  and  heated  to  130°  during  forty  hours. 
The  sulphuric  acid  solution,  separated  from  the  insoluble  part, 
boiled  with  barium  carbonate,  etc.,  reduces  Fehling's  solution. 
The  solution  also  contains  a  small  amount  of  an  acid  similar  to 
the  cerebrosic  acid  described  above.    The  cerebrose  obtained 


amounts  to  less  than  half  the  theoretical  quantity,  but  is  supple- 
mented by  a  small  portion  of  its  derivate. 

The  solid  products  of  the  chemolysis  are  coloured  brown ;  when 
warm  they  are  in  a  state  of  semifusion.  The  mass  is  gently  warmed 
with  soda  solution  and  shaken  with  ether.  It  dissolves  in  the 
ether  without  residue,  imparting  to  it  a  deep  brown  colour.  The 
ether  is  distilled  off  and  the  residue  treated  with  hot  absolute 
alcohol.  This  solvent  leaves  a  small  quantity  of  caramel  of 
psychosin  as  a  brown  mass,  and  dissolves  a  quantity  of  slightly 
coloured  matter.  The  solution  is  decolorised  with  animal  charcoal, 
and  precipitated  with  a  little  sulphuric  acid  dissolved  in  absolute 
alcohol.  The  precipitate  is  isolated,  washed  with  ether,  and  dried. 
It  gives  no  purple  reaction  with  oil  of  vitriol  alone,  thus  proving 
the  absence  of  psychosin,  but  with  a  solution  of  cane-sugar  or 
cerebrose  the  sulphuric  acid  solution  gives  a  brilliant  purple 
reaction.    The  precipitate  is  therefore  sphingosin  sulphate. 

The  alcoholic  mother-liquor  of  the  sphingosin  sulphate  contains 
some  matter  in  solution,  which  gives,  after  removal  of  the  alcohol, 
a  purple  reaction  with  oil  of  vitriol  by  itself.  It  is  some  psychosin 
which  has  resisted  the  chemolytic  action  of  the  dilute  sulphuric 

The  chemolysis  of  psychosin  by  sulphuric  acid  therefore  takes 
place  according  to  the  equation  : 

c^^o,  +  H,o  =  cyiiA  + 

Psychosin.  Cerebrose.  Sphingosin. 

Purple  lleadion  with  Oil  of  Vitriol. — I  have  shown  that  all  the 
cerebrosides  give  with  oil  of  vitriol,  on  gentle  warming,  a  reaction, 
which  consists  in  the  formation  of  a  deep  purple  colour.  This 
reaction,  which,  when  produced  with  cane-sugar  and  oil  of  vitriol, 
is  known  as  Raspail's  or  Pettenkofer's  reaction,  and  was  for  a 
long  time  believed  to  be  specific  to  biliary  acids,  has  been  shown 
to  be  common  to  a  large  number  of  bodies  which  probably  have  a 
radicle  in  common.  But  most  of  these  bodies,  e.g.  oleic  acid, 
require  the  addition  of  sugar,  and  do  not  give  the  purple  with 
oil  of  vitriol  alone.  Now,  the  known  cerebrosides  are  distinguished 
from  the  biliary  and  fatty  bodies  by  the  faculty  of  giving  the 
purple  reaction  under  tAvo  different  sets  of  conditions.  They 
give  it  with  oil  of  vitriol  alone,  on  gentle  warming,  after  a  little 
time  of  standing  ;  and  they  give  it  quicker  if  with  the  oil  of 


vitriol  a  little  sugar  is  at  once  added.  Now  we  know  that  all 
these  bodies  contain  the  radicle  of  the  sagar  cerebrose,  which,  as 
I  have  shown,  gives  with  pure  gtykocholic  acid  and  sulphuric 
acid  a  brilliant  Pettenkofer  reaction,  and  is  therefore  capable  of 
replacing  cane-sugar  to  its  full  value  in  this  process.  It  is  there- 
fore clear  that  the  ability  of  the  cerebrin  bodies  to  give  the  purple 
with  oil  of  vitriol  alone  has  for  one  of  its  causes  the  presence  in 
their  constitution  of  the  radicle  of  cerebrose.  That  they  react 
slower  with  sulphuric  acid  alone  than  with  sulphuric  acid  and 
sugar  added  is  perhaps  explained  by  the  facts  evolved  in  the 
chemolysis  above  described,  namely,  that  the  splitting  off  of  cere- 
brose from  the  other  radicles  requires  time. 

We  are  now  able  to  advance  the  hypothesis,  which  has  a  high 
degree  of  probability,  that  every  phrenosin-like  body  which  gives 
a  purple  reaction  with  oil  of  vitriol  alone  contains  the  radicle  of 
cerebrose  besides  that  other  radicle  which,  with  any  sugar,  cere- 
brose, or  cane-sugar,  gives  the  purple,  and  which  we  will  term 
the  oleo-cholide  radicle.  On  the  other  hand,  any  phrenosin-like 
body  which  does  not  give  the  purple  with  oil  of  vitriol  alone  may 
contain  either  the  cerebrose  or  the  oleo-cholide  radicle.  If,  on 
addition  of  sugar,  it  gives  the  purple,  then  it  contains  the  oleo- 
cholide  radicle  ;  if  it  does  not  give  the  purple,  then  this  radicle 
also  is  excluded. 

I  will  now  proceed  to  the  application  of  these  data  to  the  test- 
ing of  the  chemolytic  products  above  described.  Sphingosin, 
with  oil  of  vitriol  at  a  very  gentle  heat,  dissolves  and  becomes  a 
little  yellow.  But  no  purple  colour  is  produced.  On  addition  of 
cane-sugar  or  of  cerebrose  in  highly  concentrated  solution  the 
purple  is  immediately  struck.  Psychosin,  with  oil  of  vitriol  at  a 
very  gentle  heat,  becomes  yellow  and  brownish  while  dissolving, 
and  then  the  purple  colour  appears  without  any  addition  of  sugar. 
Consequently  there  is  a  piind  facie  presumption  that  psychosin 
still  contains  the  cerebrose,  while  from  sphingosin  it  is  detached. 
We  have  already  seen  how  well  this  presumption,  derived  from 
the  chemical  reactions  of  these  bodies,  is  supported  by  their 
relative  chemical  formulae.  The  reaction  can  consequently  be 
used  for  demonstrating  the  purity  or  impurity  of  any  specimen  of 
sphingosin  as  regards  its  freedom  from  or  contamination  with 
substances  capable  of  yielding  cerebrose  with  oil  of  vitriol.  The 
substances  most  likely  to  remain  mixed  with   sphingosin  in 


small  quantity  are  those  of  which  it  is  a  cleavage-product, 
and  more  particularly  psychosin,  which,  like  sphingosin,  is  an 

Isolation  of  Hie  Purple  Products. — The  purple  bodies  produced  in 
the  reaction  of  the  cerebrin-products  described  in  the  foregoing 
pages  are,  under  certain  conditions,  soluble  in  chloroform  ;  it  is 
necessary  to  place  the  mixture  in  bottles  carefully  stoppered,  and 
keep  them  anhydrous  by  excess  of  oil  of  vitriol.  The  clear  dry 
chloroform  solution  can  be  distilled  from  dry  vessels  boiling,  and 
leaves  the  purple  product  behind.  The  residue  dissolves  in  new 
chloroform  with  a  finer  purple  colour  than  before  and  completely. 
A  little  water  added  to  the  purple  chloroform  solution  makes  it 
turbid,  and  destroys  the  colour  completely  in  a  few  minutes. 
The  purple,  which  has  been  redissolved  after  the  removal  of  the 
first  chloroform  by  distillation,  is  destroyed  by  water  instan- 

Caramel  of  Psychosin. — Experiment. — 0-3615  g.  heated  at  110° 
C,  in  the  apparatus  used  in  the  other  cases,  lost  '021  g.,  and 
the  CaClg  gained  -0225  g.  At  this  temperature  the  substance 
became  brown  and  caked.  It  was  then  heated  to  160°  C,  when 
it  fused  completely,  losing  -0145  g.,  the  gain  being  at  the  same 
time  -0185  g.  At  210'  C.  it  had  lost  -021  g.,  while  the  CaCl2 
had  gained  the  same  amount.  On  cooling,  it  split  up  into  flakes, 
which  were  only  partially  soluble  in  ether.  At  210°  0.  the 
current  of  air  was  stopped,  as  there  was  a  slight  deposit  of 
volatile  matter  on  the  cooler  parts  of  the  tube.  The  current  was 
resumed  as  the  caramel  cooled. 

Tahular  View  of  the  Data  concerning  the  Caramel  of  Psychosin. 




per  cent. 



per  cent. 















4-43  ' 

Bemarls  on  the  Caramels. — The  preliminary  experiment  on  the 
action  of  heat  upon  phrenosin  showed  a  loss  of  10-2  per  cent., 
which  is  equal  to  4-03  molecles  of  water  on  the  formula 
C^jHwgNOs.  The  maximum  loss  which  phrenosin  experiences  in 
the  experiments  described  later  is  similar  in  amount,  but  the 


water  collected  does  not  tally  with  it.  It  is  therefore  clear  that 
some  oxidation  takes  place  in  the  substance  under  caramelisation  ; 
this  hypothesis  does  not,  however,  completely  explain  the  dis- 
crepancies. In  future  experiments  the  operation  should  be 
carried  on  in  a  current  of  neutral  gas,  such  as  hydrogen  or 
nitrogen,  or  in  carbonic  acid. 

/.  Intermediate  Products  of  the  Chemolysis  of  the  Cerehrosides  tvith 
Sulphuric  Acid:  Hydrated  Phrenosin,  j^sthesin,  Psychosin. 

The  decomposition  of  the  cerehrosides  by  barita  ensues  in  a 
much  shorter  time  than  by  acids.  The  products,  though  essen- 
tially the  same  in  both  processes,  are  differently  distributed, 
and  are  split  off  at  different  times  and  in  a  different  order.  It 
is  essential  to  know  all  those  products  which  are  intermediate, 
in  the  first  instance,  because  without  them  the  formulae  of  the 
decomposition  cannot  be  made  evident  with  all  necessary  detail, 
and  secondly,  because  small  quantities  of  these  intermediate  pro- 
ducts mostly  outlast  the  chemolytic  process,  and  then  occur  as 
impurities  in  the  final  products  or  are  left  as  residues  incapable 
of  purification  and  analysis. 

The  first  event  in  the  sulphuric  acid  chemolysis  of  phrenosin  is 
])voh2ih\y  hydration.  The  next  event  is  t\iQ  splitting  off  of  the  cere- 
brose.  This,  in  the  water  solution,  ensues  very  slowly,  while  the 
first  hydration  is  probably  more  quickly  attained. 

The  remainder  of  the  radicles,  minus  the  cerebrose,  do  yet  hold 
together  for  a  longer  time  before  they-  split  up  into  sphingosin, 
fatty  acids,  and  other  bodies. 

Forty -four  g.  of  mixed  cerehrosides  were  boiled  in  water,  and 
pressed  through  a  cloth.  To  the  homogeneous  paste  40  cc.  of 
oil  of  vitriol,  already  diluted  with  the  amount  of  water  necessary 
to  prevent  overheating,  were  added.  The  mixture  was  now 
boiled,  and  curdled  immediately.  Boiling  was  continued  for 
nearly  an  hour,  when,  the  liquid  containing  much  sugar  and 
becoming  more  coloured,  heat  was  withdrawn. 

The  curdled  cerebrin  matter  was  transparent  and  soft  while  hot, 
slightly  coloured  red,  and  became  solid  and  white  immediately 
on  cooling.  In  order  to  remove  any  fatty  acids  which  it  might 
contain,  it  was,  after  removal  of  all  sulphuric  acid,  suspended  in 
ammonia  water,  and  precipitated  by  barium  chloride.    The  curdy 


precipitate  was  found  to  be  almost  entirely  soluble  in  hot  spirit, 
and  to  contain  hardly  any  fatty  salt  insoluble  in  spirit. 

The  spirit  solution  filtered  hot  through  a  heated  funnel  imme- 
diately deposited  white  crystals.  These,  under  the  microscope, 
were  seen  to  consist  of  two  bodies,  one  in  needles,  another  in 
crystalline  balls.  The  deposit  from  spirit  was  isolated  and  sus- 
pended in  ether. 

A  hody  dissolved  which  crystallised  from  the  evaporating  ether 
in  apparently  curved  needles,  which  will  presently  be  more  closely 
defined.  Another  body  remained  insoluble  in  ether,  and  on 
combustion  left  some  barita.  This  latter  will  not  be  considered 
any  further  in  this  place. 

Crystallised  soluble  in  Ether  Product. — JEsthesin.  —  The  ether 
solution  was  distilled  to  a  small  bulk,  and  then  allowed  to  crys- 
tallise. It  formed  a  voluminous  white  mass  consisting  entirely 
of  crystals,  which  were  uniform  and  showed  many  angular  plates. 
They  were  collected  on  a  filter  and  drained  of  mother-liquor  by 
stirring.  While  wet  they  fused  on  the  water-bath  in  the  mother- 
liquor  adhering  to  them,  but  became  completely  dry  without 
much  discoloration,  and  were  solid  and  waxy,  therefore  not 
fusible  below  90^  Recrystallised  slowly  from  a  dilute  solution 
in  ether,  the  crystals  are  seen  to  be  hexagonal  plates,  more  or 
less  regular,  but  whether  or  not  the  six  angles  of  the  hexagons 
are  equal  cannot  be  determined.  The  plates  are  saucer-shaped, 
and  this  produces  the  appearance  of  the  curved  or  sickle-shaped 
needles  when  the  bodies  are  seen  sideways  and  the  lower  edge 
is  out  of  focus.  The  plates  are  scarcely  visible  when  they  lie 
flat  on  the  glass.  They  are  distinctly  recognised  with  all  the 
details  when  they  are  made  to  roll  edgeways  over  the  field 
(Chinese  hats). 

The  dry  crystals  dissolve  in  oil  of  vitriol  and  assume  a  yel- 
lowish colour,  but  no  purple  colour.  Cane-sugar  added  to  this 
produces  the  purple  reaction  soluble  in  chloroform  and  yielding 
a  specific  spectrum ;  consequently,  this  body  contains  the  oleo- 
cholide  radicle,  but  not  the  cerebrose  radicle.  It  was  now 
analysed.  Between  80°  and  150°  0*1825  g.  lost  in  three  stages 
5  mgrs.  in  Aveight;  the  remainder  burnt  left  1  mgr.  incombustible 
residue.  The  dry  powder  fritted  a  little,  and  at  82°  to  83°  became 
a  waxy  transparent  mass.  It  fused  to  a  liquid  at  110°,  but  did 
not  become  opaque  until  again  cooled  to  71°.    By  recrystallisation 


its  nitrogen,  which  at  first  was  2*70  per  cent.,  could  be  depressed 
to  2-35.  After  purification  and  crystallisation  from  absolute 
alcohol  and  from  pure  ether,  in  both  of  which  it  was  soluble  in 
the  cold,  it  crystallised  in  the  same  hexagonal  plates.  Heated  to 
150°  it  became  coloured,  and  exhaled  an  odour  of  burnt  fat.  For 
analysis  it  was  heated  to  100°  for  three  hours,  and  gave  results 
which  are  represented  in  the  following  summary  : 


-f-At.  Wgts. 

-4-N  =  l. 

















These  results  prove  that  sesthesin  is  an  intermediate  product 
of  chemolysis ;  it  does  not  contain  the  cerebrose  radicle,  as  is 
evident  from  the  low  quantity  of  oxigen  it  contains,  and  it  still 
retains  the  oleo-cholide  radicle,  as  is  evident  from  its  yielding  the 
purple  reaction  when  sugar  is  added.  It  therefore  behaves  like 
a  sphingosin  to  which  a  fatty  acid  radicle  is  still  combined.  The 
nitrogen  is  a  little  too  low ;  that  is  to  say,  sesthesin  is  already 
mixed  with  a  trace  of  fatty  acid,  but  the  oxigen  stands  to  carbon 
in  the  relation  of  about  3  atoms  to  35  atoms.  Hence  the  hypo- 
thesis that  sesthesin  is  a  compound  of  sphingosin  and  neurostearic 
acid  gains  a  high  degree  of  probability,  thus  : 

Sphingosin.      +  Neurostearic  acid.         JEsthesin.  Water, 

G^,'^,    +     G^^,     =    C^coNO^  +  H,0. 
If  now  to  sesthesin  we  add  a  molecle  of"  cerebrose,  we  obtain — 
^sthesin.  Cerebrose.  Phrenosin.  Water. 

The  fatty  acid  radicle  contained  in  sesthesin  is  supposed  to  be 
neurostearic  acid. 



Theory  of  a 







35  C  420 



35  C  420 


69  H  69 



71  H  71 


1  N  14 



1  N  14 


3  0  48 



4  0  64 







The  aesthesin  analysed  did,  therefore,  yet  contain  about  half  a 
molecle  of  water.    The  body  seems  to  be  a  base. 

g.  Chemolysis  of  Fhrenosin  hy  Sulphuric  Acid  in  Alcoholic  Solution: 
Formation  of  Ethylic  Neurostearate. 

The  Process. — Sixty-five  g.  phrenosin  were  suspended  in  1500  cc. 
of  spirit  of  85  per  cent,  strength,  and  200  cc.  of  oil  of  vitriol 
gradually  added  while  the  mixture  was  well  agitated.  The  hot 
mixture,  on  which  an  oily  matter  floated,  was  then  boiled  for 
two  hours  and  a  half  in  such  a  manner  that  the  volatilised  alcohol 
was  condensed  and  ran  back  again  into  the  fluid.  On  cooling,  the 
oily  layer  solidified,  and  a  slight  deposit  formed  in  the  underlying 
fluid.  The  insoluble  and  deposited  parts  were  separated  by  filtra- 
tion from  the  acid  solution  and  dissolved  in  ether ;  the  ethereal 
solution  was  agitated  with  dilute  solution  of  caustic  soda,  by  which 
a  small  quantity  of  fatty  acid  was  removed  as  soda  salt.  The 
clarified  ether  solution  was  distilled,  and  the  residue  was  re- 
peatedly crystallised  from  absolute  alcohol.  From  this  solvent  it 
was  deposited  in  small  shining  crystals,  which  were  very  soluble 
in  hot  alcohol,  but  very  little  in  cold.  The  recrystallised  matter 
fused  at  56°  C,  but  the  manner  of  its  fusion  seemed  to  indicate 
an  admixture  of  a  less  fusil)le  with  a  more  fusible  body.  It  was 
subjected  to  a  preliminary  elementary  analysis  by  the  vacuum 
method  with  the  following  result :  0  0872  g.  gave  0-1080  g. 
HoO,  0-2443  g.  CO.,,  and  0-00043  g.  nitrogen.  The  small  amount 
of  nitrogen  was  evidently  due  to  the  presence  of  a  small  quantity 
of  a  nitrogenised  substance  which  was  at  once  eliminated  by  the 
process  of  distillation  in  vacuo  about  to  be  described.  The  re- 
crystallised  body  was  mixed  with  glass  powder  and  placed  in  a 
glass  tube  closed  at  one  end.  This  was  then  bent  dov/nwards  at 
a  point  beyond  the  mixture,  and  a  little  further  on  bent  again 
upwards,  drawn  out  and  connected  air-tight  to  a  mercurial  air- 
pump.  The  air  was  then  completely  pumped  out,  and  heat 
cautiously  applied  until  the  matter  was  distilled  into  the  V-shaped 
part  of  the  tube  ;  this  was  effected  without  the  evolution  of  any 
gas  and  without  a  trace  of  charring.  When  at  the  end  of  the 
distillation  the  slight  residue  in  the  glass  powder  began  to  discolour 
and  to  evolve  gas,  the  operation  was  stopped. 

Ncurostearic  Ether,  C2oH^^02. — The  distilled  matter  was  of  the 
colour  and  consistence  of  bleached  beeswax.    It  melted  at  52°  C. 


On  analysis  it  gave  numbers  agreeing  with  those  demanded  by  the 
formula  C^qH^qO^.    It  contained  no  trace  of  nitrogen. 

Theory.  Found. 

Atoms.  Percents. 

240            76-93  76-69 

40            12-82  12-95 

O,          32            10-26  10-36 

312  100-00  10000 

The  body  is  ethylic  neurostearate  {Q.2^r)Q-^^.^fi.2^  as  was 
proved  by  the  following  experiment :  4*5  g.  of  the  ether,  which 
had  been  completely  freed  from  any  adhering  alcohol  by  fusion  at 
110°  during  several  days,  were  enclosed  in  the  platinum  chemo- 
lyser  with  concentrated  soda  ley,  and  heated  to  100°  for  eight 
hours,  during  which  the  chemolyser  was  frequently  shaken.  The 
caustic  solution  when  quite  cold  was  poured  upon  a  filter  of  glass 
wool,  and  by  this  means  the  soap,  which  was  quite  insoluble  in 
the  concentrated  ley,  was  separated  from  the  excess  of-  alkali ; 
and,  after  rinsing  with  cold,  was  dissolved  in  a  large  quantity  of 
boiling  water.  It  gave  a  clear  solution.  A  portion  of  this  solu- 
tion, precipitated  hot  with  barium  chloride,  gave  a  barium  salt. 
This  was  converted  into  free  acid,  which  was  dried  and  dissolved 
in  ether.  On  concentration,  the  ether  gave  a  crystallisation  of 
perfectly  white  neurostearic  acid  in  a  characteristic  form.  The 
ethereal  mother-liquor  crystallised  similarl}^  in  cauliflower  masses 
to  the  last  drop.  This  acid  fused  at  84°  C.  It  was  dried  by 
fusion  at  100°  C,  and  analysed  with  the  following  results  : 
Theory.  Found. 

Atoms.        At.  Wgts.  Percents.  Percents. 

216            76-06  75-94 

Hg^             36            12-68  12-64 

Oo              32            11-26  11-42 

284  100-00  100-00 

The  concentrated  soda  ley  employed  in  this  chemolysis  of  the 
neurostearic  "ether  was  examined  for  alcohol.  It  was  distilled,  the 
distillate  enclosed  hermetically  in  a  glass  tube  with  excess  of 
chromic  and  sulphuric  acids,  and  heated  for  six  hours  to  100°. 
The  chromic  acid  was  partially  reduced,  and  on  distillation  of  the 
fluid  an  acid  distillate  was  obtained.    This,  after  boiling  with 



barium  carbonate,  and  evaporation  to  dryness,  gave  0-32  g.  dry 
barium  acetate,  giving  a  red  coloration  Avith  ferric  chloride,  evolv- 
ing the  pungent  fumes  of  acetic  acid  when  moistened  with  oil  of 
vitriol,  and  giving  the  fragrant  odour  of  acetic  ether  with  alcohol 
and  oil  of  vitriol. 

Psychosin  Sulphate. — The  alcoholic  mixture  of  sulphuric  acid 
and  other  decomposition  products  from  which  the  neurostearic 
ether  had  been  removed  by  filtration,  was  treated  with  caustic 
lime  in  powder,  and  the  liquid,  now  free  from  sulphuric  acid, 
filtered  from  the  gypsum  and  some  calcium  neurostearate  which 
was  mixed  with  the  precipitate.    The  alcoholic  solution  was  dis- 
tilled, and,  after  the  alcohol  had  passed  off,  left  a  voluminous 
white  pasty  mass  of  free  psychosin.    This  was  dissolved  in  hydro- 
chloric acid  and  ether,  and  thus  separated  from  the  impurities,  of 
which  sulphovinate  of  calcium  was  the  principal  one.    The  ether 
solution  of  psychosin  hydrochlorate  was  freed  from  ether  by  dis- 
tillation, the  residual  salt  dissolved  in  water,  and  allowed  to  stand 
in  the  .  cold.    It  deposited  colourless  crystalline  plates,  masses  of 
fine  microscopic  crystals  of  extreme  tenuity,  but  showing  geometric 
definition  of  sides  and. angles;  these  easily  redissolved  if  the 
liquid  was  allowed  to  rise  in  temperature.    Filtration  was  there- 
fore effected  in  the  cold.    These  crystals  consisted  of  pure  sj^hin- 
gosin  hydrochlorate,  as  was  proved  by  isolation,  decomposition 
with  caustic  potash  in  the  hot,  extraction  of  the  base  with  ether, 
solution  of  the  base,  after  distillation  of  the  ether,  in  absolute 
alcohol,  and  precipitation  of  the  sulphate  by  oil  of  vitriol  dissolved 
in  absolute  alcohol.    The  psychosin  in  the  solution  was  identified 
by  isolation  and  all  the  characteristic  tests. 

A.  Action  of  Heat  upon  Phrenosin ;  Formation  of  a  Caramel. 

Freliminary  Experiments. — Some  preliminary  experiments  for 
the  study  of  the  action  of  heat  upon  phrenosin  may  be  here  again 
referred  to  (see  'Eeports,'  etc.,  New  Series,  No.  III.,  1874,  p.  191). 
'0-5290  g.  lost,  on  drying  between  18°  and  70°  C,  0'0084  hygro- 
scopic water,  and  the  remaining  0-520G  g.  was  considered  as  dry 
substance.  After  two  hours'  exposure  to  a  heat  of  97°  C.  in  an 
air-bath  it  became  slightly  yellow,  and  had  lost  0-0016  g.  After 
three  hours'  exposure  to  101°  it  had  remained  of  the  same  colour 
and  weight.    After  two  hours'  exposure  to  1 45°  it  had  become 


very  dark,  almost  black  in  colour,  and  superficially  fused,  and  had 
lost  0*0080  g.  After  heating  to  158°  during  three  hours  it  had 
become  thoroughly  fused,  and  of  a  reddish,  almost  transparent 
aspect ;  it  had  lost  0*0120  g.  in  weight.  After  four  hours  at 
177°  0.  it  had  become  blacker  and  less  transparent,  and  gave  out 
a  faint  odour  of  burnt  meat :  it  had  lost  at  this  stage  0*0317  g. 
Thus  the  phrenosin  had  lost  in  four  stages  0*0533  g.,  or  10*2  per 
cent,  in  weight.  After  cooling,  it  was  hard  and  brittle.  On 
boiling  a  piece  in  absolute  alcohol,  only  a  trifling  amount  of 
matter  dissolved,  colouring  the  solution  slighty  yellow.  On  the 
other  hand,  it  readily  dissolved  in  ether ;  the  solution  had  a  dark 
reddish-brown  colour.  A  little  of  the  phrenosin  was  heated  in  a 
test-tube  over  the  naked  flame.  It  fused,  turned  dark,  and 
evolved  water  with  ebullition,  similar  to  sugar  passing  into 
caramel.  The  water,  which  condensed  in  the  upper  part  of  the 
tube,  had  an  acid  reaction,  and  reduced  copper  solution.  The 
fused  matter  became  hard  on  cooling,  was  but  slightly  soluble  in 
boiling  alcohol,  but  readily  soluble  in  ether ;  from  the  latter 
solution  it  was  reprecipitated  by  alcohol.' 

Similar  exj^eriments  were  now  instituted,  with  a  view  of  in- 
creasing the  accuracy  of  results  and  the  knowledge  concerning 
the  constitution  and  function  of  phrenosin. 

First  Experiment. — Some  phrenosin  was  dried  in  a  current  of 
air  at  100°  C,  in  a  Liebig's  drying-tube  placed  in  a  paraffin  bath, 
connected  at  each  end  with  a  chloride  of  calcium  drying-tube,  one 
to  dry  the  air  before  it  entered  the  tube,  and  the  other  to  arrest 
the  moisture  from  the  phrenosin  evolved  during  the  operation. 
A  drying-tube  filled  with  glass  saturated  with  sulphuric  acid 
served  to  prevent  moisture  from  the  water-pump  diffusing  back- 
wards into  the  chloride  of  calcium  tube. 

The  dry  phrenosin  weighed  1*216  g.  The  temperature  was 
raised  to  150°  C,  a  current  of  dry  air  passing  meanwhile.  When 
the  tube  containing  the  phrenosin  was  weighed,  it  was  found  to 
be  still  of  the  same  weight  as  at  the  beginning  of  the  experiment ; 
but  the  chloride  of  calcium  tube  had  gained  *019  g.,  a  fact  which 
can  only  be  explained  by  oxidation  of  the  phrenosin.  At  this 
stage  the  phrenosin  became  brownish-white  in  colour,  but  did  not 
fuse.  The  temperature  being  now  raised  to  160°,  the  phrenosin 
melted  into  a  brown  mass,  and  on  being  weighed  was  found  to. 


have  lost  -014  g.,  the  chloride  of  calcium  tube  having  gained  the 
same  amount.  The  temperature  was  then  rapidly  raised  to 
200°  C,  but  there  was  no  longer  a  current  of  air  allowed  to  pass 
through,  in  order  to  retard  as  much  as  j^ossible  the  evolution  of 
volatile  matter.  On  cooling,  air  was  passed  through  as  before, 
and  the  tube  on  being  weighed  showed  a  loss  of  0  054  g.,  the 
chloride  of  calcium  tube  having  only  gained  0*050  g.  The  tem- 
perature was  now  finally  increased  to  240'  C,  with  the  same 
precautions  against  escape  of  volatile  matter  as  before.  Volatile 
matters  were  now,  however,  evolved  which  slightly  blackened  the 
sulphuric  acid  ;  and  when  the  connections  of  the  apparatus  were 
severed,  a  smell  of  burnt  sugar  was  perceived.  The  tube  showed 
a  loss  of  0*080  g.,  while  the  chloride  of  calcium  tube  had  gained 
0*056  g. 

Thus  in  the  whole  operation  the  tube  had  lost  12*17  per  cent,, 
while  the  chloride  of  calcium  had  gained  11*425  per  cent.  Taking 
the  formula  of  phrenosin  as  C^^HyglSTOg,  the  molecular  weight  of 
it  would,  be  713.  The  preceding  figures  would  then  give  us, 
taking  the  loss  as  12*17  per  cent.,  a  loss  of  4*82  molecles  of 
water;  and,  taking  the  gain  as  11*425  per  cent,  a  loss  of  4*52 

Second  Experiment. — Some  phrenosin  was  dried  at  100°  C,  the 
weight  of  the  dry  body  being  0*789  g.  The  temperature  of  the 
tube  was  now  raised  to  200°  C,  and  kept  at  that  point  for  two 
hours,  air  being  passed  through  only  on  cooling  below  150'.  No 
volatile  matters  were  carried  into  the  sulphuric  acid  tube,  though 
a  slight  sublimation  of  volatile  matter  on  to  the  cooler  parts  of 
the  tube  took  place.  On  weighing,  the  tube  was  found  to  have 
lost  0*0456  g.,  and  the  chloride  of  calcium  had  gained  0*054  g. 
The  heating  was  now  continued  at  200°  for  four  hours,  to  try  the 
effect  of  time  on  the  operation,  air  being  passed  through  only  on 
cooling.  The  loss  was  now  0*0365,  and  the  gain  0*0365.  The 
totals  in  percents.  were  a  loss  on  the  part  of  phrenosin  of  10*14 
per  cent,  or  4  02  molecles,  and  a  gain  on  the  part  of  the  calcium 
chloride  of  11*47  per  cent,  or  4*54  molecles  of  water. 

The  greater  portion  of  the  caramel  obtained  in  both  these  ex- 
periments was  soluble  in  ether;  the  first  caramel  was  not  so 
perfectly  soluble  as  the  second,  on  account  of  the  greater  tem- 
perature to  which  the  former  had  been  raised. 


Tabular  View  of  the  Data  concerning  Caramel  of  Phrenosin. 

I^^y       T^rv^r.  '^""^""K   A/r  1    1      Percent.      Total  Molecles 

Amount.  ^^^P-       Loss,     per  cent.  Molecles.     (.^i^.     Pei"  cent.      jj  q_ 


1-216      1.50  -00       —  —  1-56  —  — 

—  160  M5       —  —  1-15  —  — 
200  4-44       —  —  4-11  —  — 

—  240  6-58  12-17  4-82  4-605  11-425  4-52 
-789      200  5-89       —  —  6-85  —  — 

—  200  4-25  10-14  5-02  4-62  11-47  4-54 

i.  Special  Reactions  of  Phrenosin. 

Reaction  of  Phrenosin  with  Oil  of  Vitriol^  Chloroform  and  Glacial 
Acetic  Acid;  Spectral  Phenomena  of  the  Product. — Phrenosin  from 
the  brain  of  man  was  suspended  in  chloroform,  and  sulphuric  acid 
added  ;  this  was  allowed  to  stand  five  minutes,  and  the  chloroform 
was  then  decanted ;  it  remained  white  and  clear.  On  being 
allowed  to  stand  over  the  sulphuric  acid  all  night  the  chloro- 
form was  still  colourless,  but  the  sulphuric  acid  was  darker ;  the 
latter  was  dissolved  in  glacial  acetic  acid  with  a  little  sulphuric 
acid  in  order  to  dissolve  some  red  particles.  The  solution  so 
produced  had  a  magnificent  red  colour,  and  presented  spectra  as 
follows :  In  a  concentrated  solution  red  only  passed.  This 
solution  had  a  green  fluorescence.  More  diluted  three  bands 
appeared,  one  between  D  and  E,  a  second  between  E  and  F,  and 
a  third  between  F  and  Gr. 

Reaction  of  Phrenosin  with  Pettenkofer's  Test ;  and  Spectrum  of  its 
Product. — Phrenosin  from  the  brain  of  man  was  dissolved  in  boiling 
chloroform ;  it  became  turbid  on  cooling,  but  did  not  become  con- 
gealed. This  solution  was  now  mixed  with  sulphuric  acid  and 
sugar,  then  stirred  and  repeatedly  breathed  upon ;  it  formed 
purple  oily  drops,  but  no  solution  took  place.  These  drops  were 
insoluble  in  glacial  acetic  acid,  but  dissolved  rapidly  in  chloro- 
form. The  solution,  kept  anhydrous  by  sulphuric  acid,  presented 
the  following  spectrum  with  Drummond's  light :  a  narrow  band 
between  C  and  D,  and  a  wide  deep  black  band  between  D  and  h. 
These  reactions  of  phrenosin  are  very  similar  to  those  of  kerasin 
to  be  described.  They  are  also  very  similar  to  those  of  oleic 


k.  Theory  of  the  Chemical  Constitution  of  Phrenosin. 

Although  the  average  of  the  analyses  of  phrenosin  leads  to  data 
from  which  the  true  formula  of  its  composition  can  be  derived,  it 
is  a  great  advantage  to  be  able  to  prove  the  true  formula  by  the 
aid  of  the  formulae  of  the  products  of  decomposition.  If  phrenosin 
had  never  been  analysed  by  itself,  its  formula  could  be  predicted 
by  means  of  the  synthesis  of  its  cleavage-products,  according  to 
the  followinsf  calculation : 

1  molecle  of  sphingosin    -  .  .  Cj^Hg^NO^. 

+  1      ,,      of  neurostearic  acid  -  -  C^gHg^  O^. 

+ 1      „      of  cerebrose      -  -  "  H^^  ^o- 

—  2  molecles  of  water  -       -  -  -  0.,. 

leave  one  molecle  of  phrenosin        -  C^^H-gNOg. 
Arranged  analytically  the  equation  would  be  the  following  : 
C„H,,NOs  +  2(H,0)  =  C,^,,m,  +  C,,U,fi,  +  C,U,.fi,. 
Of  this  phrenosin  the  atomic  and  percentic  theory  is  the  follow 

Theory.  Found  mean. 

^  '  , 

Atoms.  Percents.  Percents. 

41  C  492  69-000  67  957 

79  H  79  11-080  11-426 

1  N  14  1-963  1-997 

8  0  128  17-957  18-696 

mo; : 

713  100  000 

This  phrenosin,  in  the  course  of  chemolysis,  by  taking  up  two 
molecles  of  water,  increases  its  atomic  weight  from  713  to  749, 
which  latter  figure  represents  the  sum  of  the  atomic  weights  of 
the  three  products  of  decomposition  above  enumerated.  100 
parts  of  phrenosin,  therefore,  become  105  parts  of  products.  Of 
these  39-6  parts  are  neurostearic  acid,  39-9  parts  sphingosin,  and 
25*1  parts  cerebrose. 

If  now,  with  the  aid  of  this  theory,  we  attempt  to  revise  the 
theories  formerly  given  of  some  compounds  of  phrenosin,  re- 
taining the  analytical  data,  we  obtain  a  greater  harmony  than 
before.    Thus  the  nitrited  phrenosin  shows  the  following  theory : 

Nitrited  Phrenosin  Nitrate,  C^iH^y(NO^,)NOg -f  HNO..3,  or  con- 
tracted, C^lH^gNyOiy 



41  C  492 
79  H  79 
3  N  42 
13  0  208 




in  100. 




Neurostearic  Acid  is  accurately  distinguished  from  the  isomeric 
known  common  stearic  acid  by  its  high  fusing-point  (84°  to  85^"), 
and  its  atomic  weight  is  well  fixed  by  its  ethyl  compound.  But 
its  salts  are  not  very  stable  nor  very  precise  bodies,  or  are 
mixtures,  so  that  it  has  hitherto  proved  impossible  to  use  them  for 
stoichiometric  purposes.    The  theory  of  this  acid  is  the  following  : 

Theory.  Found 

18  C  216 
36  H  36 
2  0  32 





in  Crystallised  Acid. 


in  Acid  from  Ether, 


100  00 


The  ethylic  compound  of  this  acid  is  a  very  precise  body ;  it  is 
Neurostearic  Ether  or  ethylic  neurostearate,  and  its  theory  is  the 








20  C  240 



40  H  40 

12-82  • 


2  0  32 






The  dissolved  formula  is 

Sphingosin  is  a  strong  base,  and  gives  the  most  precise  compounds 
of  any  products  of  the  decomposition  of  phrenosin.  Its  theory  is 
the  following : 



17  C  204 

35  H  35 

IN  14 

2  0  32 



Percents.  found 

in  Sulphate, 
Acid  deducted. 





Sphingosin  Sulphate,  2(Ci^H35NO^)  +  H2SO4. 





Percent  s 

34  C  408 



72  H  72 



2  N  28 



4  0  64 



IS      32  ) 
4  0      64  1 




100-00  . 


Cerehrose,  CgH^^Ojj,  is  a  sugar  characterised  by  its  crystallisation, 
its  optical  power  (its  specific  or  limited  rotation  being +  70°  40'), 
and  its  reducing  power  over  cupro-potassic  tartrate.  Its  theory 
is  the  following  : 







C  72 




H  12 




0  96 






Under  certain  conditions  which  have  been  described  above, 
cerebrose  is  changed  into  an  acid  isomeric  with  cerebrose,  and 
therefore  of  the  formula  C^H^^O,^.  This  cerehrosic  acid  is  dibasic, 
i.e.f  contains  two  atoms  of  hydrogen  replaceable  by  metals.  The 
theory  of  the  cerebrosate  of  barium  is  the  following  : 

Theory.  Found. 

Atoms.  Percents.  Percents. 

6  C      72  22-85  24-53 

10  H     10  3-17  3-2 

1  Ba  137  43-49  43 -5 

6  0      96  30-49 


This  acid  is  remarkable  in  this,  that  it  has  not  got  any  reducing 
power  over  potassio-cupric  tartrate,  but  on  the  other  hand  gives 
with  an  oleo-cholide  radicle,  e.g.  sphingosin,  and  oil  of  vitriol  the 
purple  reaction  in  the  same  manner  as  cerebrose. 

Psychosin,  C.yfl^r^'NOj,  is  the  cerebroside  of  sphingosin  ;  it  is 
crystallisable  from  alcohol ;  it  is  an  alkaloid,  but  of  less  pro- 


nounced  character  than  sphingosin  ;  it  forms  salts  with  acids,  which 
are  more  or  less  soluble  in  water,  the  hydrochlorate  being  very 
soluble  indeed.  By  this  solubility  in  cold  water  it  can  be  separated 
almost  completely  from  the  hydrochlorate  of  sphingosin,  which 
crystallises  from  cold  water,  or  cold  solution  of  psychosin  hydro- 


Theory  Percents. 






























One  hundred  parts  of  psychosin  on  chemolysis  should  take  up 
4-02  parts  of  water  (one  molecle),  and  then  split  up  into  40-29 
parts  of  cerebrose  and  63-75  parts  of  sphingosin. 

The  hydrochlorate  is  completely  precipitated  by  excess  of 
hydrochloric  acid.  Many  compounds  may  be  expected  to  be 
obtained,  as  psychosin  exhibits  numerous  promising  reactions. 
It  gives  the  oleo-cholide  reaction  with  oil  of  vitriol  alone,  showing 
that  it  contains  the  cerebrose  and  sphingosin  radicles. 

The  Caramels  of  the  cerebrosides  are,  like  the  caramels  of  the 
sugars,  produced  by  the  expulsion  of  water  under  the  influence  of 
heat.  They  are  all  soluble  in  ether,  insoluble  in  alcohol  and  in 
water,  and  of  a  deep  brown  colour.  The  following  formulae  are 
hypothetical  and  interimistic,  although,  derived  from  the  data  of 
the  experiments  given  above. 

Caramel  of  Phrenosin,  C^Ji>j^O^,  formed  from  a  molecle  of 
phrenosin,  C^^H^gNOg,  by  the  loss  of  four  molecles  of  H^O. 

Caramel  of  Psychosin,  C^gHg^NOg,  formed  from  a  molecle  of  psy- 
chosin, by  the  loss  of  four  molecles  of  water. 

A  small  quantity  of  caramel  is  formed  during  every  chemolysis 
of  any  of  the  cerebroside  principles,  with  acid  or  with  alkali,  even 
during  the  chemolysis  of  psychosin  with  dilute  sulphuric  acid. 
There  may  be  several  varieties  of  caramel  of  each  principle  pro- 
duced by  the  loss  of  one,  two,  three,  or  four  molecles  of  water. 
There  might  be  mixed  with  some  preparations  of  phrenosin  parti- 
cular varieties  of  phrenosin,  in  very  small  quantity,  containing  in 
place  of  the  neurostearic  another  fatty  acid  radicle.    And  there 


might  be  mixed  with  an  hypothetical  di-neurostearyl-sphingosyl- 
cerebroside,  a  similarly  constituted  body  containing  in  place  of 
one  or  both  molecles  of  neiirostearyl  other  fatty  acid  radicles,  and 
in  place  of  the  sphingosyl  another  nitrogenised  radicle  ;  in  this 
respect  the  nitrogenised  principles  might  imitate  the  phosphoriscd 
principles,  which  derive  their  principal  differences  from  the  dif- 
ferent fatty  acid  radicles  which  they  contain.  I  think  it  even 
very  probable  that  some  of  the  phosphoriscd  bodies  which  cling 
so  pertinaciously  to  the  nitrogenised  ones  owe  their  similarity  to 
these  latter,  both  in  shape  and  chemical  properties,  to  the  fact  of 
their  containing  one  or  other  or  both  of  the  radicles  of  the  nitro- 
genised bodies  which  appear  as  neurostearic  acid  and  sphingosin. 

3.  Kerasin,  the  Second  Cerebroside:  its  Isolation  and 

Tntrodudion. — As  in  the  case  of  phrenosin.  I  have,  up  to  the 
present  moment,  not  succeeded  in  isolating  a  preparation  of 
kerasin  which,  on  analysis  of  a  sufficient  quantity,  proved  to  be 
free  from  phosphorus.  The  preparation  which  yielded  the  lowest 
amount  of  phosphorus,  namel}^  0-08  per  cent.  (8  parts  of  phos- 
phorus in  10,000  parts  of  kerasin),  weighed  only  4  g.,  so  that 
after  six  quantations,  for  which  the  materials  were  taken  from 
these  4  g.,  there  was  not  left  material  enough  to  be  employed  in 
a  systematic  attempt  at  chemolysis  of  this  particular  specimen. 
But  I  have  examined  a  considerable  number  of  preparations  of 
kerasin  which  contained  more  of  the  phosphoriscd  impurity,  not 
exceeding  0-4  per  cent,  of  P  ;  and  some  of  these  specimens  have 
yielded  information  which,  when  compared  with  the  information 
derived  from  the  purest  specimens,  seemed  to  be  independent  of  the 
influence  of  the  thus  far  unavoidable  impurity.  But  the  informa- 
tion, though  decisive  as  far  as  it  goes,  is  only  fragmentary  as 
regards  the  entire  problem  ;  and  I  therefore  point  out  that  what 
I  have  to  report  is  only  the  beginning  of  a  great  research  to  be 
made  in  the  future. 

Mode  of  Isolation. — The  ox  white  matter,  which  had  been  ex- 
tracted with  ether  and  dried,  was  pulverised  and  dissolved  in  hot 
absolute  alcohol  ;  the  solution  was  decanted  from  the  fused  mass 
of  stearoconot  which  formed,  and  allowed  to  deposit  the  dissolved 
matter  by  cooling.  The  deposit  formed  after  the  first  hour  was 
isolated,  as  was  also  another  which  formed  after  the  second  hour ; 


a  third  gelatinous-looking  precipitate  formed  over-night,  and  from 
this  the  absolute  alcohol  solution  was  filtered.  On  standing  for  a 
few  days  in  stoppered  bottles,  this  solution  deposited  a  gelatinous 
membranous  mass,  mainly  consisting  of  Jcerasin.  This  was  re- 
moved by  the  filter,  and  the  filtrate,  which  contained  much 
sphingomyelin  in  solution,  was  treated  with  CdCl^.  The  white 
bulky  precipitate  of  sphingomyelin  CdCl2  was  filtered  off,  washed, 
exhausted  with  ether,  and  further  treated  as  is  described  else- 
where. It  may  be  mentioned  here  that  the  principal  bulk  of 
sphingomyelin  is  obtained  in  this  manner  and  at  this  stage.  The 
alcohol  filtered  from  the  sphingomyelin  CdCl2  precipitate  after 
concentration  deposited  a  mixture  of  CdCl2  salt,  cholesterin, 
and  kerasin,  the  latter  two  being  present  in  very  small  pro- 
portions. , 

Mode  of  Purification. — Kerasin  obtained  as  above  is  a  soft  white 
gelatinous  mass,  consisting  of  larger  and  smaller  balls,  which 
under  the  microscope  are  seen  uniformly  to  consist  of  wavy 
masses  of  needles  so  thin  that  it  may  be  said  they  possess  only 
one  diameter— namely,  length.  The  gelatinous  state  is  apparently 
entirely  due  to  this  peculiarity  of  the  fine  needles  enclosing  a 
large  amount  of  alcohol.  No  amorphous  matter  whatever  is  seen 
mixed  with  it,  but  here  and  there  a  few  rosettes  of  phrenosin, 
strikingly  differentiated  from  the  kerasin. 

The  whole  of  the  kerasin  was  dissolved  three  times  in  boiling 
absolute  alcohol,  and,  after  cooling  to  crystallisation,  washed  and 
pressed  free  from  mother-liquor.  This,  after  the  third  operation, 
was  free  from  sphingomyelin,  as  shown  by  the  absence  of  reaction 
with  PtCl^,  and  CdCl^.  The  solution  of  kerasin  was  also  free 
from  sphingomyelin,  CdCl^  giving  no  precipitate  with  it. 

The  kerasin  was  now  dissolved  in  a  fourth  quantity  of  pure 
absolute  alcohol,  and  allowed  to  crystallise.  It  was  found  by 
microscopic  examination  that  after  three  hours  much  kerasin  in 
wavy  crystallised  masses,  but  no  phrenosin  in  rosettes,  had  been 
deposited.  The  crystals  were  consequently  isolated,  pressed, 
again  recrystallised,  collected  on  a  filter,  and  dried  in  vacuo. 
This  preparation  was  analysed  with  the  result  stated  below. 

After  this  preparation  had  been  removed,  at  the  end  of  the 
third  hour,  from  the  mother-liquor,  the  latter  on  standing  de- 
posited a  mixture  of  much  kerasin  in  wavy  needles,  with  some 
rosettes  of  phrenosin.    This  mixture  could  by  recrystallisation 


not  be  completely  separated.  A  third  ultimate  precipitate  seemed 
to  consist  mainly  of  phrenosin,  with  much  kerasin,  which  could 
also  not  be  purified  hj  mere  recrystallisation. 

Special  Consideration  of  the  Properties  of  Kerasin  tvhich  are  r)iade 
use  of  for  Its  Isolation. — The  properties  of  kerasin  which  are  made 
use  of  for  its  isolation  are  the  following :  It  is  easily  soluble  in 
hot  spirit,  and  almost  insoluble  in  cold  ;  it  tarries  to  deposit  from 
this  solution  for  a  long  time,  and  if  its  amount  does  not  exceed 
1  part  in  321  parts  of  spirit,  it  is  not  deposited  at  all  above  28°, 
and  below  that  temj)erature  very  slowly.  By  this  peculiarity  it 
is  separated  from  phrenosin  and  sphingomyelin,  the  latter  parti- 
cularly when  it  is  in  the  state  of  cadmium  chloride  salt.  Kerasin 
does  not  combine  with  lead  ;  by  this  property  it  is  separated  from 
myelin  and  the  cerebrinacides,  which  combine  with  lead.  It  does 
not  combine  with  cadmium  chloride,  and  by  this  reagent  is 
liberated  from  sphingomyelin,  amidomyelin,  and  paramyelin, 
which  combine  with  it.  It  is  not  soluble  in  ether,  either  cold  or 
boiling ;  by  cold  ether  the  kephalins  and  lecithins  are  extracted 
from  it,  and  by  boiling  ether,  krinosin.  Kerasin  swells  when  left 
in  contact  with  ether  for  some  time.  In  that  state  it  must  not  be 
allowed  to  dry  on  paper,  as  it  contracts  and  becomes  hard,  and 
adheres  so  strongly  to  the  paper  that  it  cannot  be  separated  from 
it  without  retaining  fragments  of  paper  in  its  substance.  Kerasin, 
crystallised  from  absolute  alcohol  in  a  flask,  if  allowed  to  dry 
slowly  in  the  flask  after  the  alcohol  has  been  poured  off,  becomes 
white  and  pulverulent,  so  as  to  crumble  off  the  sides  of  the  glass, 
and  does  hardly  become  waxy.  When  deposited  from  watery 
solvents,  or  removed  from  contact  with  even  anhydrous  ether,  it 
becomes  on  drying  hard  and  horny,  or  waxy,  and  difficult  to 

Solubility  of  Kerasin  in  Different  Quantities  of  Spirit. — 3-8878  g. 
human  kerasin,  dried  on  the  water-bath,  we^e  dissolved  in  500  cc. 
hot  spirit  of  84  per  cent,  strength.  On  cooling  of  the  solution  a 
deposit  of  kerasin  began  to  form  at  40°,  and  continued  to  increase 
while  the  temperature  sank.  200  cc.  spirit  were  added  to  the 
mixture,  and  the  deposit  was  redissolved  by  the  application  of 
heat.  On  being  again  allowed  to  become  cool,  it  now  became 
turbid,  and  began  to  make  a  deposit  at  35^  A  further  addition 
of  50  cc.  of  s})irit  reduced  the  depositing-point  to  34°.  Another 
100  cc.  reduced  the  crystallising-point  to  33°.    A  further  100  cc. 


depressed  the  temperature  of  crystallisation  to  32°.  Three  more 
additions  of  100  cc.  spirit  each  depressed  the  crystallising-point 
to  30%  29°,  and  28°  respectively.  Altogether,  therefore,  3-8878  g. 
kerasin  required  1250  cc.  of  spirit  to  be  kept  in  solution  at  28' ; 
one  part  of  kerasin  required  321  parts  of  spirit  to  remain  in  solu- 
tion at  28°. 

Fifty  cc.  of  a  solution  of  kerasin  in  spirit,  which  began  to 
crystallise  at  28°,  were  at  that  temperature  filtered  and  evaporated 
to  dryness  on  the  water-bath.  The  residue  weighed  0*1558  g. ; 
therefore  1  g.  kerasin  required  320*92  cc.  of  spirit  at  28°  for 

Solubility  of  Kerasin  in  Aceton. — At  the  ordinary  temperature 
of  the  air,  100  cc.  of  aceton  dissolve  0*1576  g.  kerasin;  at  the 
boiling  temperature  of  aceton,  100  cc.  dissolve  1*0510  g.  kerasin. 

Solubility  of  Kerasin  in  Benzol. — When  moist  kerasin  is  shaken 
with  large  volumes  of  benzol,  it  remains  as  an  insoluble  gelatinous 
transparent  mass.  The  filtered  benzol  leaves  no  residue  on  dis- 
tillation. When  kerasin  and  benzol  are  warmed,  a  perfect  solution 
is  produced,  which  can  be  filtered  hot.  On  cooling,  all  kerasin  is 
deposited,  and  the  benzol  leaves  no  residue  on  distillation.  This 
solvent,  therefore,  may  serve  for  the  separation  of  bodies  which 
are  soluble  in  cold  benzol. 

Reactions  of  Kerasin. — Both  human  and  bovine  kerasin  give  a 
deep  purple  with  oil  of  vitriol  and  sugar  at  once ;  with  oil  of 
vitriol  alone,  a  paler  purple  after  long  standing.  Kerasin  from 
ox-brains  is  dissolved  in  boiling  chloroform.  On  cooling,  it  con- 
geals to  a  glassy  solid.  A  portion  of  this  is  stirred  with  a  drop  of 
cane-sugar  solution  and  a  small  quantity  of  sulphuric  acid.  At 
first  it  becomes  yellowish,  and  at  last  purple.  The  colour  is  in 
drops,  and  not  dissolved ;  it  is  not  soluble  in  glacial  acetic  acid, 
but  chloroform  dissolves  the  whole  to  a  purple  solution.  This 
before  the  spectroscope  shows  a  narrow  band  between  C  and  D, 
and  a  deep  black  band  extending  from  D  to  F.  The  acid  solu- 
tion below  the  chloroform,  is  yellowish,  fluorescing  green.  When 
some  kerasin  is  dissolved  in  chloroform,  and  sulphuric  acid 
added,  all  the  kerasin  passes  into  the  acid,  and  the  chloroform 
remains  colourless  :  this  proves  that  the  kerasin  is  free  from 
cholesterin.  When  this  mixture  is  allowed  to  stand,  a  brownish- 
red  mass  rises  to  the  top  of  the  acid  ;  sugar  added  to  this  makes 
it  redder.    W^hen  this  is  placed  in  a  dish  and  the  chloroform 


evaporated,  oily  deposits  form  of  increased  redness,  the  oxigen  of 
the  air  evidently  tending  to  make  them  purple ;  but  this  purple 
product  is  now  insoluble  both  in  acetic  acid  and  chloroform,  singly 
or  united. 

Kerasin,  in  a  Liebig's  drying-tube,  heated  in  an  oil-bath  to 
from  100°  to  150°  in  a  current  of  dry  air,  loses  about  4  molecles  of 
water,  and  is  transformed  into  a  brown  matter  soluble  in  ether, 
insoluble  in  alcohol  (caramel  of  kerasin). 

Elementary  Analyses  and  Theory  of  Kerasin.— A.  specimen  of 
kerasin  from  the  ox  obtained  from  70  g.  of  the  principle  by  fre- 
quent fractional  .recrystallisation,  and  containing  yet  0*01  per 
cent.  P,  was  analysed,  and  yielded  the  first  group  of  data  in  the 
synopsis  below. 

A  specimen  of  human  kerasin  was  repeatedly  crystallised  from 
absolute  alcohol,  allowed  to  dry,  and  crumble  in  flask,  and  dried 
over  oil  of  vitriol  in  vacuo.  It  contained  0  073  per  cent.  P;  it 
gave  on  analysis  the  second  set  of  data  in  the  synopsis. 

If  we  group  these  analyses  so  as  to  let  the  highest  nitrogen 
come  first,  we  obtain  the  following  hypotheses  : 

Synopsis  of  Analyses  of  Kerasin  from  Ox. 


-^  At.  Wgt. 

C  69-54 



H  11-69 



N  1-92 



0  16-85 




Synopsis  of  Analyses  of  Kerasin 

from  Man. 

Percents.  -t- 

At.  Wgt. 

~  N=l. 

C  69-01 



H  11-44 



N        1  -90 



0  17-65 




Synopsis  of  Analyses  of  Kerasin  from  Ox,  made  in  1874. 


-i-  At.  Wgt. 

N  = 






J 1-395 












The  two  first  sets  of  analyses  are  probably  to  be  preferred,  and 
it  is  very  probable  that  the  formula  of  kerasin  is  C42Hg5N03,  or 
C^^HggNOg ;  any  formula  giving  oxygen  as  eight  atoms  has  theory 
in  its  favour,  as  we  shall  see  below.  But  in  any  case  the  formula 
cannot  be  established  by  analysis  alone  ;  chemolyses  of  kerasin 
and  analyses  of  the  cleavage  products  are  required  to  enable  us 
to  form  a  final  opinion  as  regards  its  chemical  constitution. 

Chemolysis  of  Kerasin. — Kerasin  is  a  cerebroside,  and  yields 
cerebrose  by  chemolysis  with  dilute  sulphuric  acid.  In  some 
chemolyses  with  barita,  the  study  of  the  acid  products  of  the 
chemolysis  could  not  be  accomplished  for  want  of  quantity. 
But  the  basic  parts  were  identified  in  two  forms,  and  the  presence 
of  cerebrose  w^as  incidentally  confirmed. 

Four  g.  of  kerasin  were  mixed  with  8  g.  of  barita  hydrate 
crystals,  and  sufficient  water  to  produce  a  thin  paste.  The 
mixture  was  enclosed  in  a  tube  and  heated  during  fourteen  hours 
to  100°.  The  watery  solution,  free  from  barita,  gave  a  reaction 
for  cerebrose.  The  insoluble  in  water  part  was  extracted  with 
alcohol ;  the  concentrated  solution  yielded  a  precipitate  of  a  sul- 
phate. Another  part  of  the  matter  was  not  precipitated  by  sul- 
phuric acid,  but  remained  in  solution.  It  was  shown  to  be 
psychosin,  like  the  base  of  the  precipitated  sulphate.  This  sul- 
phate dried  to  a  horny  mass  on  the  filter,  and  did  not  remain 
pulverulent  like  sphingosin  sulphate.  It  was  dissolved  in  boiling 
water,  with  which  it  formed  a  clear  solution,  and  precipitated 
with  a  large  excess  of  caustic  alkali.  It  did  not  rise  to  the  top 
like  an  oil,  as  sphingosin  does,  on  heat  being  applied,  but  formed 
a  jelly  or  semi-soap  ;  with  more  potash  it  became  emulged  ;  the 
solution  became  turbid  on  cooling ;  ether  extracted  nothing  from 
it.  The  only  way  to  extract  the  alkaloid  was  to  acidify  the  solu- 
tion with  sulphuric  acid,  and  add  phospliomolybdic  acid  to  it. 
The  precipitate,  after  decomposition  with  barita,  yielded  to  spirit 
the  psychosin,  which  was  transformed  into  sulphate  and  analysed. 

Analyses  of  the  Sulphate  obtained,  and  Comparison  luith  the  Com- 
position of  Psychosin  Sulijhate  and  Sphingosin  Sidphate. 

Found  in  Product  from       Psychosin  Sulphate.       Sphinsfosin  Sulphate. 
Kerasin.  2(Co3H4.5N07)H2SOj.  2(Ci7H35NO.,)H2S04. 

C       54-67  "   55-65   "  60-11 

H      10-48  9-27  10  78 

SO^    10-59  9-67  14-37 



As  the  sulphate  yields  Raspail's  reaction  without  sugar  being 
added,  it  must  be  psychosin,  mixed,  however,  with  a  small  trace 
of  sphingosin. 

It  follows  from  the  foregoing  that  kerasic,  like  its  principal 
companion  phrenosin,  is  a  cerebroside,  namely,  a  body  which  con 
tains  the  sugar  cerehrose,  combined  with  at  least  two  other  radicles. 
Of  these,  one  is  probably  sphingosin,  the  alkaloid  obtained  from 
phrenosin.  The  other  is  certainly  a  fatty  acid,  but  the  nature  and 
composition  of  this  acid  have  not  yet  been  perfectly  ascertained. 


1.  General  Observations  on  the  Subgroup. 

The  following  account  of  preliminary  observations  may  serve 
as  the  basis  for  future  more  perfect  inquiries.  Of  some  bodies 
the  mere  existence  has  been  ascertained,  and  they  have  not  been 
definitively  isolated.  Others  have  been  isolated  in  a  state  of 
artificial  combination  Avith  reagents.  Two  have  been  isolated  in 
such  a  state  of  semi-crystallisation  (spherocrystals  and  groups  of 
microscopic  needles)  that  their  appearance  and  behaviour  give 
some  probability  to  the  assumption  that  they  are  approximately 
pure.  But  the  only  final  control  of  actual  composition,  quanta- 
tion  of  atomic  weight  by  combination  and  demonstration  of  con- 
stitution by  chemolysis  could  not  yet  be  applied  to  them. 

Separation  of  these  Substances  from  the  Cerebrin  Mixture  by  Lead 
Acetate  and  Ammonia. — This  process  has  already  been  described, 
but  may  here  again  be  noticed.  The  cerebin  mixture,  exhausted 
with  ether,  is  dissolved  in  hot  spirit,  and  to  the  solution  a  hot 
solution  in  spirit  of  acetate  of  lead  is  added  as  long  as  a  precipi- 
tate is  produced.  Ammonia  is  then  added,  and  when  neither 
lead  acetate  nor  ammonia  produce  any  further  precipitate,  the 
solution  is  filtered  hot  from  the  precipitate.  The  latter  contains 
the  bodies  here  to  be  considered,  while  the  spirit  solution  con- 
tains the  cerebrosides  and  other  substances  which  do  not  combine 
with  lead  under  these  circumstances. 

The  Lead  Salts. — The  insoluble  precipitate  formed  during  the 
purification  of  phrenosin  by  the  lead  acetate  treatment  is  ex- 
hausted with  hot  85  per  cent,  spirit  to  remove  all  phrenosin  and 



kerasin.  It  is  then  dried,  powdered,  and  extracted  with  cold 
benzol.  A  portion  of  the  lead  salts  dissolved,  another  remained 

2.  Cerebrinic  Acid  :  its  Isolation  and  Properties. 

The  benzol  extracts  were  evaporated  to  dryness,  and  the  dr}^ 
residue  was  powdered  and  suspended  in  85  per  cent,  spirit.  The 
spirit  was  saturated  with  hydrothion  while  being  gradually  raised 
to  the  boiling-point,  and  the  lead  sulphide  filtered  off.  On  cooling 
a  white  body  was  deposited,  which  consisted  mainly  of  cerebrinic 
acid.  This  was  collected  on  a  filter,  purified  by  recrystallisation 
from  absolute  alcohol,  and  dried  in  vacuo.  It  gave  a  weak  purple 
reaction  with  oil  of  vitriol  alone.  Under  the  microscope  it  ap- 
peared to  consist  of  small  needles.  It  was  soluble  in  hot  benzol, 
and  was  thrown  down  on  cooling  as  a  gelatinous  mass.  It  did 
not  blacken  at  100°  C.  On  elementary  analysis  it  gave  data 
which  are  collated  in  the  following  table  : 

a.          b.          c.  d. 

Nitrogen  per  cent.       1-5         —          —  1-68 

Carbon,  per  cent.         —  66 '47  67*54  — 

Hydrogen,  per  cent.     —  11-355  11 '37  — 

Caramel  of  Cerebrinic  Acid — First  Experiment. — 1*613  g.  of  dry 
cerebrinic  acid  were  heated  to  210°  C,  in  a  current  of  air  for  one 
hour.  The  tube  lost  0*122  g.,  or  7*55  per  cent. ;  and  the  chloride 
of  calcium  gained  0*103  g,,  or  6*38  per  cent.  Calculated  on  a 
formula  (hypothetical)  of  C^gH^^gNOg,  and  a  molecular  weight  of 
979,  these  figures  would  give  a  loss  of  4*1  molecles  of  water,  as 
judged  by  the  diminution  of  the  weight  of  the  cerebrinic  acid, 
and  they  would  correspond  to  3*47  molecles  of  H2O  if  only  the 
gain  of  weight  of  the  water- catching  tube  were  taken  into  con- 
"  sideration. 

Second  Experiment. — 1*221  g.  of  dry  cerebrinic  acid  was  heated 
to  160°  C.  The  substance  melted  completely,  and  lost  0*030  g., 
the  chloride  of  calcium  gaining  0*033  g.  The  temperature  was 
now  raised  to  200°  C,  and  the  current  of  air  was  passed  only 
when  the  tube  cooled.  The  loss  and  gain  respectively  were  0*065  g. 
and  0*056  g.  The  total  loss  was  thus  7*77  per  cent.,  or  4*227 
molecles;  and  the  gain  was  7*30  per  cent.,  or  3*97  molecles  of 



Third  Exjjenmeni— 1-073  g.  at  150^  C.  lost  0-012  g.,  and  the 
chloride  of  calcium  tube  gained  0*019  g.  At  this  temperature 
the  cerebrinic  acid  melted.  At  200°  C.  it  lost  0*0965  g.,  and  the 
chloride  of  calcium  gained  0*080  g.  The  total  percentages  were 
10-12  per  cent,  loss,  or  5*5molecles,  and  9*23  per  cent,  gain,  or 
5*00  molecles  of  water. 

Fourth  Experiment. — 0*779  g.  of  dry  cerebrinic  acid  at  I'lS'^  lost 
0*006  g,,  and  the  chloride  of  calcium  gained  0*0125  g.  At  180° 
the  substance  was  completely  melted,  and  lost  0*033  g.,  while  the 
chloride  of  calcium  gained  0*037  g.  At  210°,  the  current  of  air 
being  stopped  as  before  until  the  tube  had  somewhat  cooled  down, 
the  loss  was  0*0535  g.,  and  the  gain  0*030  g.  The  totals  lead  to 
a  loss  of  11  67  per  cent.,  or  6*347  molecles  of  water,  and  to  a  gain  of 
9*98  per  cent.,  or  5*43  molecles.  Oxidation  may,  as  in  the  former 
case,  account  for  this  discrepancy. 

These  caramels  also  were  almost  entirely  soluble  in  ether. 

Tabular  Vieiv  of  the  Data  concerning  the  Caramels  of  Cerebrinic 



Per  cent. 




per  cent. 

of  H2O. 


































*  -779 














3.  Sulphurised  Principles,  Sphero-cerebrin,  and  others. 

Mode  of  sejjarating  these  Substances  from  the  Cerebrin  Mixture. — 
The  cerebrin  mixture  (that  part  of  the  white  matter  which 
remains  insoluble  when  it  is  exhausted  with  ether)  is  dissolved  in 
hot  spirit,  and  to  the  solution  a  hot  solution  in  spirit  of  acetate  of 
lead  is  added  as  long  as  a  precipitate  is  j^roduced.  Ultimately  a 
little  ammonia  is  added,  and  the  solution  is  filtered  hot  from  the 
precipitate.  The  latter  contains  the  bodies  here  to  be  con- 


The  crude  Lead  Compound^  to  he  hereafter  referred  to  as  'Bark  Lead 
Salt/  Ox-Cerehrins. — This  body  was  exhausted  with  boiling  spirit, 
the  extraction  being  repeated  an  indefinite  number  of  times ;  all 
that  which  spirit  extracted  will  not  be  considered  any  further  in 
this  place.  The  matter  insoluble  in  spirit  was  now  extracted 
with  benzol  until  nothing  further  dissolved.  There  remained  in- 
soluble a  lead  compound  which  had  a  peculiar  ash-grey  colour,  re- 
minding the  observer  at  once  of  the  probability  that  a  small  part 
of  the  lead  had  by  some  means  or  other  been  converted  into 

-  Quantation  of  Lead  and  Organic  Matter  and  of  Sulphur  and  Phos- 
phorus in  the  Dark  Lead  Salt. — {a)  1*2992  g.  decomposed  with 
hydrothion  in  hot  spirit  gave  0"3490  PbS,  equal  to  23-27  per 
cent.  Pb,  and  therefore  about  76 '73  per  cent,  of  organic  matter. 
{h)  1-4826  g.  burnt  with  soda  and  mercuric  oxide  in  a  tube,  etc., 
gave  0-1749  BaSO^,  equal  to  1*62  per  cent.  S,  and  0*1574  pyro- 
phosphate of  magnesia,  equal  to  2-97  per  cent.  P. 

Attempt  to  isolate  the  sulphurised  Principle,  the  Presence  of  which 
tvas  demonstrated  hj  the  foregoing  Analysis. — The  alcoholic  solution 
which  had  been  obtained  in  analysis  [a)  of  the  foregoing  para- 
graph deposited  much  organic  matter  on  cooling  ;  this  was  redis- 
solved  by  heat,  and  in  the  hot  solution  a  precipitate  was  i3roduced 
by  barita  water.  The  precipitate  was  exhausted  by  boiling  spirit, 
and  the  extracts  were  disregarded.  The  matter  insoluble  in  spirit 
was  dissolved  in  benzol,  and  the  solution  separated  from  the 
insoluble  portion.  The  benzol  solution  was  concentrated  by  dis- 
tillation, and  precipitated  by  absolute  alcohol.  The  precipitated 
body  was  dried  and  analysed. 

0-3068  (being  almost  the  entire  product  of  this  first  operation) 
fused  with  nitre-flux,  etc.,  gave  0-0288  BaSO^=l-32  per  cent.  S. 

This  experiment  proves  that  the  sulphurised  principle  contained 
in  the  lead  salt  can  be  transformed  into  a  barium  salt  soluble  in 
benzol.  This  salt  contained  less  sulphur  than  the  original  lead 
salt.  When  it  is  compared  to  other  sulphurised  barium  compounds 
of  similar  properties,  which  I  shall  have  to  describe  below,  it  is 
seen  that  in  the  former  the  sulphur  amounts  to  a  much  lesser 
percentage  than  in  the  latter.  From  a  third  series  of  observations 
to  be  related,  it  will  be  seen  that  the  brains  of  young  animals 
contain  at  least  one  sulphur  body,  which  is  so  labile  that  on 
standing  in  its  ether  solution  it  deposits  sulphur  in  the  metalloid 



state,  and  in  crystals  too,  which  are  needles  as  well  as  octahedra. 
AVe  have  therefore  three  distinct  aper(;us,  proving  the  presence  of 
sulphur  compounds  (other  than  albuminous  ones)  in  the  brain. 

Decomposition  of  the  Dark  Lead  Salt  (Ox-Cerehrins)  hij  Oxalic  Acid  ' 
in  boiling  Spirit. — It  was  evident  that  for  the  study  of  the  sulphur 
compound  in  the  lead  salt  the  application  of  sulphuretted  hydrogen, 
although  apparently  quite  successful  in  the  above  experiment, 
would  have  to  be  avoided.  A  quantity  of  the  salt  was  therefore 
boiled  with  double  that  amount  of  crystallised  oxalic  acid,  which 
theory  indicated  as  necessary  for  the  transformation  of  all  lead 
into  oxalate,  in  a  flask  fixed  to  a  refluent  cooler,  until  the  salt  ap- 
peared white  and  all  grey  colour  had  disappeared.  The  solution 
was  now  filtered  from  the  precipitate. 

InwluhU  Lead  Salt  [Oxalate). — It  was  exhausted  with  spirit, 
then  washed  with  boiling  water,  suspended  in  water,  and  treated 
-with  dilute  nitric  acid.  On  heat  being  applied  a  reaction  ensued, 
the  oxalate  dissolved,  and  a  small  quantity  of  lead  sulphate  re- 
mained insoluble.  It  weighed  0-0348  g.,  equal  to  0-0037  g.  S  in 
20  g.  salt,  or  0-0185  per  cent.  S  in  lead  salt.  This  shows  that  of 
-the  1'62  per  cent.  S  contained  in  the  lead  salt,  only  a  minute 
proportion  can  be  present  as  sulphuric  acid,  or  in  the  shape  of  a 
metallic  sulphate.  Possibly  even  the  small  quantity  found  was 
derived  from  the  oxidation  of  the  black  sulphide,  which  gives  to 
the  salt  its  dark  colour. 

The  Organic  Matter  from  the  Lead  Salt  (total  mixture  of  at  least 
three  bodies)  was  crystallised  from  the  spirit  containing  the 
excess  of  oxalic  acid,  washed,  and  pressed.  It  was  next  recrys- 
tallised  from  spirit,  and  appeared  white  and  voluminous.  It  was 
analysed  in  order  to  ascertain  whether  it  contained  sulphur  and 
phosphorus,  with  the  following  result : 

(a.)  0-8668  fused  with  flux  and  caustic  soda  gave  0'0340 

BaSO^  =  0-54  per  cent.  S. 
(h.)  The  solution  filtered  from  the  BaSO^  gave,  further, 

0-0638  pyrophosphate  of  Mg,  equal  to  2-06  per  cent.  P. 

The  organic  mixture  was  now  extracted  with  cold  benzol,  and 
filtered  by  air-pressure  through  a  tubular  filter.  The  benzol  ex- 
tracted a  small  quantity  of  a  body  which  was  recrystallised  from 
spirit  and  crystallised  in  needles.  The  part  insoluble  in  benzol 
was  also  recrystallised  from  spirit.  It  was  then  recrystallised 
from  hot  benzol,  and  deposited  entirely  on  cooling.   After  having 


been  freed  from  benzol  it  was  dissolved  in  about  a  litre  of  abso- 
lute alcohol,  and  cooled  to  38°.  A  body  was  deposited  in  heavy 
sphero-crystals,  and  adhered  to  the  glass,  so  that  the  solution  could 
be  easily  decanted  clear  from  it.  This  was  repeated,  and  all 
crystals  were  collected.  They  represent  the  body  which  in  the 
following  is  termed  splierocerehrin. 

4.  Spherocerebrin. 
The  name  is  intended  to  indicate  that  the  body  is  a  cerebrin 
crystallising  in  sphero-crystals.  It  was  twice  crystallised  frac- 
tionally from  absolute  alcohol.  The  solution  having  been  filtered 
clear,  was  now  allowed  to  cool,  while  the  temperature  was  read 
off  by  an  immersed  thermometer ;  it  began  to  form  a  deposit  at 
50°,  of  which  the  main  bulk  came  down  between  43°  and  41°. 
When  the  deposition  had  ceased,  the  spherocerebrin  was 
filtered  off. 

Seen  under  the  microscope,  it  appears  in  round  balls  of  very 
uniform  size,  which  all  have  a  peculiar  three-branched  mark  in 
the  round  field.  When  the  balls  are  rolled,  it  is  seen  that  they 
contain  three  wedge-shaped  fans  each ;  the  side  of  such  a  fan 
shows  radiating  needles ;  three  such  wedges  are  united  with 
their  sharp  straight  edges  at  a  line  representing  the  diameter  of 
the  ball.  By  gentle  pressure  the  balls  break  almost  regularly 
into  the  three  wedge-shaped  segments. 

Spherocerebrin  with  oil  of  vitriol,  on  standing,  gives  only  a 
very  feeble  reddish  colour  attached  to  flakes.  It  is  free  from 
sulphur,  and  contains  only  unweighable  traces  of  phosph(^rus 
(when  0*4462  were  analysed).  On  elementary  analysis  it  gives 
data  which  are  collated  in  the  following  synopsis  : 

Percents,  Atoms. 

C         62-75  58 

H        11-08  123 

N          1-23  1 

O         24-94  17-3 


In  its  main  features  spherocerebrin  resembles  cerebrinic  acid, 
but  it  contains  over  this  (theory  C^gH^j^NOc,)  an  excess  of  8H 
and  80,  or  8  hydroxyls.  Spherocerebrin  differs,  therefore,  from 
cerebrinic  acid  not  only  by  its  crystalline  shape,  but  also  by  its 
percentic  composition. 


5.  Principal  and  Second  Product  from  Dark  Lead  Salt. 

The  term  '  principal '  here  refers  to  quantity ;  20  g.  of  lead  salt 
gave  15-49  of  organic  product. 

The  absolute  alcohol  solution  had  been  filtered  at  40°.  At  37° 
cumuli  of  clouds  formed  under  the  bulb  of  the  thermometer.  At 
36°  the  entire  liquid  was  turbid.  At  35°  all  translucency  was  lost, 
and  the  crystals  projected  from  margin  into  fluid.  At  34°  the 
surface  became  concave,  and  the  marginal  ring  of  deposit  was  out 
of  the  fluid.  The  particles  aggregated,  and  the  fluid  became  again 
translucent.  At  32°  clouds  of  deposit  sank,  and  the  temperature 
remained  stationary  for  some  time.  At  this  point  the  deposit 
was  separated  by  filtration. 

At  30°  to  29°  a  new  cloudiness  arose,  and  a  deposit  began  to 
adhere  to  the  glass.  This  second  deposit  included  almost  all  of 
the  matter  which  was  in  solution  in  the  alcohol.  These  processes, 
therefore,  resulted  in  the  separation  of  the  organic  matter  present 
in  the  lead  com-pound  in  the  greatest  quantity,  into  two  bodies, 
one  of  which,  tlie  least  soluble  in  alcohol,  was  recrystallised  by 
itself ;  while  the  other,  the  most  soluble  in  absolute  alcohol,  was  also 
recrystallised  by  itself. 

We  have,  therefore,  at  this  stage  the  organic  matter  in  the  lead 
salt  separated  into  the  following  five  products,  arranged  in  the 
order  of  decreasing  quantities  : 

(1)  Principal  product  (not  yet  unitary)     -       -  9"59  g. 

(2)  Second  product  (more  soluble  than  foregoing)  4*04  „ 

(3)  Spherocerebrin  (least  soluble  in  alcohol)     -  1*50,, 

(4)  Needle  body  soluble  in  benzol    -       -       -  0-36  „ 

(5)  Sulphurised  compound      -       .       _       .  — 

The  Piinclpal  Product  from  Dark  Lead  Salt  (Ox-Cerebrlns). — Water 
expelled  at  90°  =  3 -4800  percent.  This  body  is  a  mixture  of  a 
phosphorised  principle  with  at  least  one  cerebrin-like  body.  If  we 
assume  all  the  phosphorus  to  be  present  in  the  shape  of  1  molecle 
of  dineurostearyl-glyceryl-neuryl-phosphatide  (C\^Hg3NP0g),  and 
deduct  this  molecle  from  the  complex  of  molecles  obtained  as  an 
empirical  formula  with  P  =  l,  then  we  obtain  a  residue  with  more 
than  7  atoms  of  nitrogen,  which,  divided  by  N  =  l  {i.e.,  by  7'36), 
gives  a  formula  not  unlike  a  cerebrin  body  with  3  nuclei  of 
neurostearic  acid,  but  with  a  quantity  of  oxigen  which  is  too 
large  to  satisfy  that  hypothesis  simply. 


Synopsis  of  the  Percentages  found  and  the  Hypotheses  applied. 



^  At.  Wgts. 

■fP  =  l. 

































We  have,  therefore,  in  the  cerebrin  residue  of  this  mixture  a 
still  larger  number  of  atoms  of  oxigen  than  in  spherocerebrin  ; 
and  this  fact  may  ultimately  lead  to  an  explanation  of  the  add 
character  of  these  compounds,  which  enables  them  to  form  firm 
compounds  with  bases,  such  as  the  cerebrosides  of  the  phrenosin 
type  do  apparently  not  form. 

The  second  (more  soluble  in  absolute  alcohol)  product,  weighing 
4-04  g.  (see  the  list  above  given),  has  not  yet  been  analysed.  It 
is  not  known  whether  it  is  or  contains  the  sulphurised  principle, 
the  existence  of  which  in  the  mixture  has  been  proved  above. 
This  inquiry  must  be  left  to  the  future. 


Introduction.  —  A  sulphurised  principle  had  already  been  dis- 
covered in  the  lead  salt  from  ox-cerebrins,  regarding  which  some 
preliminary  information  has  been  given  in  a  previous  chapter.  I 
may  also  here  repeat  the  notice  of  an  interesting  observation 
already  alluded  to  on  p.  182,  nam3ly,  the  deposition  of  metalloid 
crystallised  sulphur  from  extracts  of  brains  of  young  animals.  I 
have  lately  again  expressly  tested  the  phosphorised  substances 
which  I  have  isolated  and  named,  and  found  that  they  do  not 
contain  sulphur  as  an  essential  constituent.  A  gramme  of  pure 
kephalin  gave  only  an  unweighable  trace  of  barium  sulphate ;  and 
so  with  myelin  and  lecithin.  The  sulphur-compounds  to  be 
described  in  the  following  were  educed  with  the  aid  of  barita. 

Human  mixed  Cerehrlns. — Barita  Process  applied  for  their  Separa- 
ation.—l  applied  the  barita  process  in  this  case  in  the  hope  that. 


as  others  had  by  its  means  obtained  cerebrin  matter  free  from 
phosphorised  matter,  I  might  be  equally  successful.  My  experi- 
ment was,  however,  so  far  different  from  that  of  others,  that  I 
carefully  avoided  the  possibility  of  the  barita  acting  chemolyti- 
cally  upon  the  cerebrin-substances.  The  barita  was  therefore 
added  only  as  long  as  it  produced  a  precipitate,  and  never  in 
excess,  so  as  to  be  in  solution  in  any  appreciable  quantity.  I 
may  at  once  state  that  in  no  single  instance  out  of  four  experi- 
ments were  the  cerebrins  obtained  free  from  phosphorus. 

The  Process. — 600  g.  of  human  mixed  cerebrin-substances  were 
dissolved,  each  100  g.  in  3  litres  of  hot  alcohol.  To  the  boiling 
solution  barita-water  saturated  at  the  ordinary  temperature  was 
added  in  a  thin  stream,  so  as  not  to  interrupt  the  boiling  of  the 
alcohol.  Each  100  g.  had  450  cc.  barita-water  added.  The 
mixture  was  boiled  for  a  few  moments,  and  then  the  solution 
decanted  from  the  adhesive  preciintate.  The  latter  became 
hard  on  cooling,  and  was  detached  and  powdered.  It  was  now 
exhausted  with  boiling  alcohol ;  many  extractions  and  pulverisa- 
tions were  required  to  withdraw  all  the  matter  which  alcohol 
would  redissolve. 

Nature  of  the  Precipitate  p'ocluced  by  Barita. — The  barita-water 
does  not  produce  a  precipitate  in  the  hot  alcoholic  solution  of  the 
cerebrin  mixture  by  virtue  of  its  water,  as  was  specially  proved 
by  a  blank  experiment  with  water  only.  It  precipitates,  in  the 
first  place,  in  combination  icith  barita,  a  bod}^  (or  mixture  of  bodies) 
which  is  soluble  in  cold  benzol,  and  which  will  be  treated  of 
immediately.  At  the  same  time  there  fall  down  portions  of  the 
several  cerebrin  bodies,  phrenosin,  kerasin,  etc.,  of  which  another 
portion  remains  in  solution,  and  which  are  then  again  extracted 
from  the  precipitate  by  boiling  alcohol  without  retaining  more 
than  traces  of  barita,  precipitable  by  carbonic  acid  from  the 
alcoholic  solution.  These  latter  bodies  are  insoluble  in  cold 
benzol,  and  separable  thereby  from  the  stearoconote  or  mixture 
of  barita  compounds. 

It  must  at  once  be  pointed  out  that  the  matters  soluble  in  cold 
benzol  cannot  be  separated  from  those  insoluble  in  benzol  by  one 
operation  only.  AVhen  benzol  has  acted  upon  the  powdered 
particles  of  the  precipitate,  they  seem  to  be  covered  by  a  layer  of 
matter  insoluble  in  benzol,  which  prevents  this  solvent  from 
reaching  the  matters  soluble  in  it,  which  are  contained  in  the 


interior  of  the  particles.  It  is  therefore  necessary  to  extract  the 
j)Owder  alternately  with  cold  benzol  and  hot  alcohol,  and  suffi- 
ciently often  until  all  the  matter  is  dissolved  in  hot  alcohol  and 
cold  benzol  respectively,  or  remains  insoluble  in  either. 

Matters  soluble  in  cold  Benzol. — The  benzol  solution  obtained  in 
the  manner  described  in  the  foregoing  is  clarified  by  repose,  filtra- 
tion; and  decantation,  until  on  standing  further  it  remains  per- 
fectly clear  and  brilliant.  It  is  then  concentrated  to  a  small 
bulk,  with  the  precaution  of  keej^ing  the  solution  perfect.  It  is 
now  treated  with  absolute  alcohol  as  long  as  a  precipitate  or  tur- 
bidity is  thereby  produced.  The  precipitate  is  further  extracted 
by  boiling  absolute  alcohol,  and  dried  in  vacuo  over  oil  of  vitriol. 
The  alcoholic  mother-liquors,  particularly  those  obtained  by  boil- 
ing, contain  a  quantity  of  a  body  which  appears  in  curved  needles, 
and  therefore  will  be  designated  meanwhile  as  curved  needle  body. 

The  Earita-Compo^md  soluble  in  cold  Benzol  and  insoluble  in 
Alcohol. — It  was  dried  over  oil  of  vitriol,  at  70°  in  air-bath  before 
analysis.  It  was  a  coloured  powder,  and  on  elementary  analysis 
gave  data  which  are  collated  in  the  following  synopsis  : 

Synopsis  of  Data  : 



H-by  At.  Wgts. 

-4-by  S  =  l 


























1 :354 



The  study  of  the  relations  of  the  atoms  to  each  other  gives  at 
once  some  interesting  information.  The  sulphur  is  to  barium  as 
1 :  2,  a  fact  which  became  already  apparent  in  the  course  of  the 
analysis.  Carbon  and  hj^drogen  are  to  each  other  as  1  :  2  very 
nearly,  indicating  the  presence  in  the  compound  of  radicles  of  the 
fatty  series.  Phosphorus  and  nitrogen  stand  apparently  in  no 
relation  to  each  other,  and  in  none  to  the  sulphur  or  barium.  The 
body  is  unquestionably  a  mixture,  but  may  be  of  substances  having 
some  analogy  with  each  other.  At  least  the  bearing  of  the  pro- 
duct towards  solvents  would  support  such  an  hypothesis. 

Severed  smaller  preparations  obtained  in  a  manner  similar  to  the 


process  described  in  the  foregoing  were  analysed,  and  gave,  one, 
32-97  per  cent.  Ba,  1-06  per  cent.  S,  and  1-15  per  cent.  P  ;  the 
other,  22-14  per  cent.  Ba,  and  1*95  per  cent.  S.  They  evidently 
contained  a  lesser  proportion  of  the  sulphurised  body  than  the 
main  preparation. 


1.  Bregenin  :  ITS  Isolation  and  Properties. 

I  have  isolated  the  principle  from  both  human  and  bovine 
brains.  It  crystallises,  fuses  like  a  fat,  and  contains  nitrogen.  It 
is  extremely  soluble  in  several  reagents,  and  does  not  combine 
with  acids,  alkalies,  or  salts. 

Mode  of  Isolation. — Human  cerebrins  in  hot  alcoholic  solution 
were  treated  by  barita-water.  The  precipitated  cerebrin  bodies 
were  freed  from  barita  by  sulphuric  acid  in  alcohol  and  recrys- 
tallised.  The  most  soluble  part  contained  the  bregenin.  From 
this,  sphingomyelin  was  removed  by  cadmium  chloride ;  the 
resulting  solution  was  now  evaporated  to  dryness  and  extracted 
with  cold  benzol ;  kerasin  remained  undissolved,  while  bregenin 
and  some  other  matters  dissolved  in  the  benzol.  The  matters 
dissolved  in  benzol  were  treated  with  boiling  ether  in  a  suitable 
apparatus,  when  a  body  remained  insoluble  in  boiling  ether,  while 
two  bodies  dissolved ;  one  was  deposited  from  the  ether  on  cool- 
ing— krinosin,  to  be  described  below — while  another  remained 
dissolved  in  the  cold  ether,  namely,  bregenin.  After  removal  of 
the  ether  the  bregenin  was  dissolved  in  a  minimum  of  watery 
spirit,  filtered  hot,  and  allowed  to  crystallise.  When  after  re- 
peated crystallisation,  removal  of  the  mother-liquor  by  pressure 
between  bibulous-paper,  etc.,  the  product  consisted  of  white 
microscopic  leaflets  and  curved  needles  only,  it  was  considered 
pure  and  analysed.  Its  solution  in  spirit  does  not  give  precipi- 
tates with  cadmium  or  platinum  chloride,  or  with  lead  acetate, 
with  or  without  ammonia.  As  long,  therefore,  as  in  a  supposed 
or  reputed  solution  of  bregenin  such  precipitates  are  produced, 
they  have  to  be  removed  as  impurities.  It  is  much  more  soluble 
in  absolute  alcohol  than  in  watery  spirit ;  from  the  former  it  is 
deposited  as  a  white  solid  mass,  when  the  solution  is  concentrated ; 
when  dilute  no  deposit  at  all  may  take  place  ;  it  is  useful  to  dilute 
the  hot  alcoholic  solution  with  boiling  water  until  a  permanent 


turbidity  is  produced,  and  allow  the  mixture  to  cool.  Good 
crystals  are  obtained  from  such  a  solution. 

From  a  concentrated  spirit  solution  bregenin  crystallises  be- 
tween 50°  and  25°.  At  30°  it  is  not  completely  deposited.  A 
dilute  spirit  solution  becomes  hazy  about  40°,  and  begins  to 
crystallise  only  at  25°.  When  thus  deposited  slowly  it  appears  in 
balls  and  irregular  masses,  without  any  curved  needles.  These 
balls  can  be  transformed  into  needles  by  resolution  in  spirit  and 
rapid  cooling  down  of  the  solution. 

Physical  and  Chemical  Properties  of  Bregenin. — Besides  the 
characters  already  described  in  the  foregoing,  bregenin  has  the 
following  diagnostic  properties.  When  heated  in  a  water-oven  it 
becomes  a  little  coloured,  and  then  fuses  below  98°  to  an  oily 
fluid.  On  cooling  it  solidifies  to  a  hard  mass,  which  is  not  plastic 
like  fat  or  wax,  but  splinters,  when  cut,  in  all  directions,  and  is 
highly  electrical.  Its  fusing-point  is  between  62°  and  65°.  When 
the  fused  and  recongealed  body  in  the  filiform  tube  is  again 
heated,  it  becomes  in  part  transparent  about  62°,  but  a  core 
remains  opaque  until  a  higher  temperature  is  reached,  when  all  is 
again  fused.  This  is  due  to  the  viscosity  of  the  fused  body.  At 
the  lowest  fusing-point  it  is  transparent,  but  so  viscous  as  to  be 
hardly  mobile,  or  only  ver}^  slowly  mobile  ;  with  rising  tempera- 
ture it  becomes  as  fluid  as  a  molten  fat,  and  the  interval  between 
the  point  of  fusion  and  the  point  of  greatest  liquidity  is  consider- 
able. While  it  fuses  and  coalesces  in  the  narrow  tube  at  62°  to 
65°,  it  flows  down  the  sides  of  the  tube  only  at  75°  to  76°,  and 
then,  on  cooling,  sets  with  a  sudden  aj)pearance  of  opacity  at  58°. 
These  experiments  were  made  with  the  purest  specimen,  which 
had  been  kept  in  a  fused  state  in  the  water-oven  for  hours.  The 
bearing  of  bregenin  with  water  is  very  remarkable.  When  heated 
with  much  water,  it  fuses  like  a  fat,  on  the  top  of  it. '  But  on 
agitation  it  increases  in  bulk  and  becomes  viscogelatinous.  This 
hydration,  which  is  completed  only  on  long  standing  in  the  water, 
causes  it  to  increase  in  bulk  considerably.  When  the  swelled 
mass,  after  decantation  of  all  water,  is  heated  on  the  water-bath, 
it  contracts,  gives  out  water,  and  fuses  as  in  its  original  state 
while  all  water  is  being  evaporated. 

With  oil  of  vitriol  it  gives  no  purple  on  standing ;  the  solution 
remains  a  little  yellow.  When  sugar-syrup  is  added  to  this 
solution  it  becomes  perfectly  Avhite,  and  gives  no  vestige  of 


purple.  From  this  it  is  highly  probable  that  bregenin  does  not 
contain  the  radicles  either  of  oleic  acid  or  of  sphingosin. 

The  fused  bregenin,  when  quite  cold  again,  can  be  powdered. 
In  this  state  it  was  subjected  to  elementary  analysis,  which 
yielded  the  following  data  : 

Synoj)sis  of  Analysis  and  Theory. 

1.           2.           3.  4. 

C  73-59  73-69  73-72  — 

H  12-54:  12-92  12-56  — 

N    —        —        —  2-22 

O    —        _       _  _ 

5.  Mean.  -^At.  Wt. -^N  =  1. 

—  73-66  6-138  C^o 

—  12-64  12-64  Hgi 
2-15  2-18  0-155  N 

—  12-52  0-781  O5 


This  body,  hregenin  (from  the  Low  German  '  bregen,'  head  or 
brain,  the  latter  English  word  being  probably  a  contraction  merely 
of  bregen),  C^oHg^NO^,  is  thus  shown  to  be  approximate  in  the 
number  of  its  carbon  atoms  to  both  the  mononitrogenised  phos- 
phatides and  to  the  cerebrosides.  From  the  latter  it  is  sharply 
distinguished  by  the  low  amount  of  oxigen  which  it  contains.  It 
has  almost  exactly  the  composition  of  the  lowest  phosphatide  of 
the  lecithin  group  minus  the  phosphoric  acid,  for 

C.„H,iNO,  +  PH30,  =  C,„H,3NP03  +  H,0. 

This  might  make  us  suspect  that  it  was  derived  from  such  a 
group  by  the  mere  loss  of  phosphoric  acid,  and  consequently  that 
it  might  be  a  product  and  not  an  educt.  But  such  a  mode  of 
decomposition  of  a  phosphatide  has  no  analogy  in  the  decomposi- 
tions which  have  thus  far  been  artificially  produced.  For  in 
these  phosphorised  bodies  when  they  contained  glycerol,  this 
alcohol  remained  mainly  with  the  phosphoric  acid.  Supposing, 
as  a  mere  hypothesis,  that  bregenin  did  contain  glycerol,  then 
there  would  be  no  room  for  neurin  as  the  nitrogenised  radicle. 
In  the  absence  of  neurin,  the  nitrogenised  radicle  would  have  to 
be  one  which  does  not  occur  in  the  mononitrogenised  j^hospha- 
tides,  as  far  as  they  are  known,  and  this  would  negative  the 
suggestion  that  bregenin  might  be  derived  from  such  a  phospha- 
tide by  loss  of  phosphoric  acid.  Besides,  such  a  hypothesis  also 
presupposes  that  the  binding  radicle  is  an  alcohol  like  glycerol, 
and  that  phosphoric  acid  is  outside  the  nucleolar  arrangement,  and 
merely  attached  as  a  side-chain — a  theory  which  is  clearly  impos- 


sible  for  those  phosphatides,  which,  as  I  have  shown,  contain  no 
glycerol,  and  is  therefore  not  probable  for  the  others  which  con- 
tain it. 

Bregenin  is  obtained  by  the  foregoing  processes  in  small  quanti- 
ties only,  and  a  great  number  of  preparations  were  required  to 
yield  material  sufficiently  pure  for  analysis.  It  is  evident  that 
the  greater  part  of  the  bregenin  present  in  the  brain  must,  in  the 
process  of  extraction,  pass  into  the  alcoholic  and  ethereal  solution 
containing  lecithin  and  kephalin  ;  then  it  must  at  last  remain 
with  the  cholesterin,  where  we  accordingly  find  it.  And  it  is 
separated  from  this  only  by  treatment  with  caustic  potash,  which 
chemolyses  and  removes  the  products  of  bregenin,  while  leaving 
cholesterin  unaltered.  It  will  therefore  be  seen  that  much  further 
study  will  be  required  to  elucidate  the  physiological  quantities 
and  functions  of  this  remarkable  substance. 

2.  Krinosin,  the  Second  Eepresentative  of  the  New 
Series  of  Nitrogenised  Fats,  or  Amido-Lipotides  :  its 
Isolation  and  Properties. 

Mode  of  preparing  Krinosin. — Dry,  finely-powdered  crude  kerasin 
as  obtained  from  the  process  for  the  isolation  of  sphingomyelin 
by  cadmium  chloride  is  exhausted  in  the  ether  extraction  appa- 
ratus by  boiling  ether.  The  solvent  should  be  perfectly  anhydrous, 
and  be  renewed  from  time  to  time  until  it  extracts  nothing  more. 
For  the  extraction  is  but  slowly  completed,  and  in  most  cases 
requires  the  apparatus  to  be  kejDt  in  action  for  several  days.  The 
hot  ether  solution  deposits  krinosin  on  cooling  and  standing  as  a 
voluminous  felted  mass  of  long  microscopic  fibres,  a  wilderness  of 
mere  lines,  mostly  without  visible  end.  If  the  vessel  has  not 
been  agitated  during  the  cooling  process,  the  felted  mass  forms  a 
complete  jelly  with  the  ether.  By  strong  agitation  this  structure 
is  destroyed,  and  there  remain  only  a  few  lumps  of  felted  matter, 
looking  like  bluish  paper  pulp  in  an  abundance  of  water.  The 
fibres,  having  been  collected  on  a  filter,  dry  to  a  hard  mass,  when 
moisture,  so  easily  collected  by  the  cold  j^roduced  in  the  course  of 
the  evaporation  of  the  ether,  is  allowed  to  deposit  upon  them  ; 
when  onl}^  little  moisture  has  been  in  contact  with  them,  they 
dry  to  a  white  spongy  matter,  which  is  just  a  little  waxy  on  com- 
pression or  when  rubbed  with  the  finger-nail.  When  the  fibres, 
taken  out  of  the  anhydrous  ether,  are  dried  in  vacuo  over  oil  of 


vitriol,  they  become  a  perfectly  white  and  pulverisable  mass. 
When  this  powder  is  now  heated  in  a  water-oven  to  98°  for  some 
time,  it  becomes  somewhat  plastic  and  assumes  a  yellowish  colour. 
After  cooling  it  is  again  hard  and  perfectly  pulverisable,  but  re- 
tains the  colour  acquired  by  the  heating.  Krinosin  is  insoluble 
in  cold,  easily  soluble  in  boiling  alcohol.  It  gives  no  purple  reac- 
tion with  sulphuric  acid  alone,  and  none  with  sulphuric  acid  and 
cane-sugar.  It  is  consequently  not  a  cerebroside,  and  does  not 
contain  any  oleo-cholide  radicle. 

Synopsis  of  the  Means  of  Elementary  Analyses  and  Theory  of 


.-^At.  Wgts. 

-f-Na  =  l. 

















Consequently  the  nearest  formula  warranted  by  the  quantations 
is  C3gH-gN05.  Leaving  out  of  consideration  a  slight  excess  of 
hydrogen,  probably  due  to  the  substance  not  having  been  dried 
at  a  higher  temperature,  but  only  in  vacuo,  there  seems  good 
reason  to  suppose  that  krinosin  is  a  homologue,  in  an  isomeric 
series,  of  bregenin,  for,  we  have 

Bregenin  -  C^oHgiNO. 
Krinosin       -  C,sH..N05. 

The  homology  is  probably  not  in  the  same  series,  as  the  higher 
carbonised  bregenin  fuses  below  70°,  while  krinosin  does  not  fuse 
below  the  heat  of  boiling  water. 


1.  Alkaloids  from  the  Human  Brain. 
1.  Hypoxanthin. — The  deposit  from  the  concentrated  solution 
of  the  extractive  matters  of  the  brain  soluble  in  water  was  ex- 
hausted with  HCl ;  the  solution  was  treated  with  excess  of  silver 
nitrate,  and  the  precipitate  extracted  to  exhaustion  Avith  boiling 
dilute  nitric  acid.  The  deposited  hypoxanthin  silver  nitrate  was 
isolated  and  added  to  the  preparation  obtained  by  the  following 


The  extract  was  diluted  and  precipitated  with  mercuric  acetate. 
The  precipitate  was  washed  by  repeated  levigation  in  water,  and 
decomposed  by  H^S.  The  HgS  was  repeatedly  extracted  with 
boiling  water.  The  solutions  were  evaporated  to  a  thick  dark 
syrup,  and  filtered.  A  first  crop  of  impure  hypoxanthin  remained 
on  the  filter.    Addition  of  ammonia  produced  a  second  one. 

Both  portions  were  united,  dissolved  in  dilute  HCl,  boiled  with 
animal  charcoal,  and  reprecipitated  by  ammonia  ;  evaporation  to 
dryness  and  extraction  of  the  ammonium  chloride  with  water  left 
the  hypoxanthin,  which  was  now  also  transformed  into  silver 
nitrate  salt. 

The  united  silver  nitrate  salts  were  treated  with  ammonia 
during  several  days,  and  washed  with  ammonia-water  on  the 
filter.  The  solutions  contained  little  besides  amnionic  nitrate. 
The  last  extracts  contained  a  very  small  quantity  of  a  body 
soluble  in  ammonia,  precipitated  in  flakes  on  evaporation,  and  re 
dissolved  in  nitric  acid  on  boiling,  less  readily  precipitated  on 
cooling  than  hypoxanthin  salts,  and  therefore  more  like  xanthin 
or  guanin. 

The  silver  hypoxanthin  was  decomposed  by  H^S,  but  the  solution 
remained  black  and  unfilterable.  It  had  to  be  boiled  with  animal 
charcoal,  and  then  became  almost  colourless.  But  the  charcoal 
retained  much  hypoxanthin,  and  had  to  be  boiled  with  many  new 
portions  of  water  before  the  whole  of  the  base  which  could  be 
extracted  was  obtained.    Some  was  no  doubt  lost  in  the  charcoal. 

The  solution  was  acid  and  contained  some  phosphate  from  the 
charcoal.  It  was  treated  with  a  little  ammonia,  filtered,  evaporated 
to  dryness,  and  extracted  with  "cold  water.  The  pure  white  crystal- 
lised hypoxanthin  was  collected  on  a  filter^  washed  with  cold  water, 
and  dried.    It  formed  crystalline  white  masses  and  granules. 

2.  Second  Alkaloid. — The  mother-liquor  of  the  hypoxanthin, 
treated  with  barita  to  expel  the  ammonia,  and  then  with  carbonic 
acid,  retained  a  large  amount  of  barita  in  solution.  The  solution 
gave  precipitates  with  ferric  chloride  on  boiling,  and  with  phos- 
phomolybdic  acid.  The  barita  was  removed  by  sulphuric  acid, 
and  the  acid  solution  precipitated  by  phosphomolybdic.  The 
precipitate  was  decomposed  with  barita ;  the  filtrate  was  refiltered 
three  times  during  concentration. 

The  solution  was  acidified  with  HCl,  and  precipitated  by  AuClg. 

The  auric  chloride  salt  was  washed  with  water  (the  salt  was  very 



soluble  in  excess  of  HCl),  and  put  in  a  vacuum  to  dry.  On 
analysis  it  gave  the  data  contained  in  the  following  synopsis  : 

Synopsis  and  Computation  of  Analyses. 

Percentages . 

-7-  by  At.  Wgts. 

-V-  Au  =  l. 

N  =  l. 































It  is  at  once  evident  that  the  compound  contains  more  gold  than 
could  be  present  in  the  form  of  terchloride;  for  the  15-200  per  cent. 
CI  require  28  073  Au ;  the  excess  of  Au,  therefore,  amounts  to 
17 '670.  This  may  be  supposed  to  have  been  present  in  the  re- 
duced metallic  state.  The  salt  is,  therefore,  one  of  those  unstable 
compounds  which  decompose  during  isolation  and  drying.  Never- 
theless, the  consideration  of  the  composition  of  the  residue  will 
afford  some,  the  only,  means  of  judging  of  the  composition  of  the 
original  alkaloid.  From  the  computation  of  the  figures  obtained 
by  N  =  1,  and  deducting  the  excess  of  gold,  and  referring  the 
possible  organic  molecle  to  a  molecle  of  AuClg  (which  requires 
the  multiplication  of  the  quotients  by  N  =  1  by  5),  we  get 
CijHjgNgOg.^AuClg.  But  calculating  the  salt  which  remains 
after  deducting  the  excess  of  gold  as  a  hydrochlorate  and  auro- 
chloride,  containing  4C1  to  lAu,  we  get — 


^  At  Wgts. 

-f  Au^l. 









N  . 




CI  ) 














leading  to  a  formula  consonant  to  the  general  chemical  theory  of 
gold  double  salts  of  Ci5H,oN^O„HCl,AuCl3. 

3.  Third  Alkaloid. — This  was  left  in  the  mother-liquor  after 
removal  of  the  two  previous  bodies,  and  precipitated  by  phospho- 
molybdic  acid  from  the  acidified  liquid.  The  treatment  of  the 
precipitate  by  barita  yielded  the  alkaloid  in  solution,  retaining 
barita  not  precipitable  by  carbonic  acid.  The  solution  was  pre- 
cipitated by  absolute  alcohol.    It  remained  a  syrupy  coloured 


liquid,  and  did  not  crystallise  after  months  of  standing.  It  had 
a  marked  smell  of  human  sperma.  It  was  so  small  in  quantity 
that  no  further  research  could  be  instituted  upon  it.  After  it 
had  been  removed  from  the  mother-liquor  representing  the  ex- 
tracts obtained  by  the  mercuric  acetate  precipitation,  there 
seemed  to  be  no  further  substance  of  an  alkaloidal  nature  con- 
tained in  them. 

2.  Alkaloids  contained  in  Ox  Brain. 

The  presence  of  the  alkaloids  in  the  water-extracts  of  brain- 
matter  is  indicated  by  the  precipitates  which  they  give  with 
AuClg,  I  in  KI,  HgCl2  in  KI,  picric,  tannic,  and  phosphomolybdic 

They  may  be  obtained  as  shown  in  the  preceding  pages  by  the 
application  of  the  phosphomolybdic  acid  process,  HgCU  process, 
and  collaterally  by  the  basic  lead  acetate  process  (for  inosite). 
The  latter  process,  however,  does  not  yield  them  if  preceded  by 
the  phosphomolybdic  acid  process.  They  may  be  separated  when 
in  the  free  state  by  evaporation  to  a  syrupy  consistency  when  the 
hypoxanthin  is  deposited  while  the  second  base  is  uncrystal- 
lisable.  The  same  remarks  apply  to  a  mixture  of  the  hydro- 
chlorates,  the  hypoxanthin  compound  in  this  case  being  obtained 
in  a  crystalline  form.  Neither  the  watery  solution  of  the  free 
hypoxanthin  nor  that  of  its  hydrochlorate  gives  a  PtCl^  precipitate. 
The  hypoxanthin  may  be  purified  by  dissolving  in  boiling  water 
and  addition  of  excess  of  silver  nitrate  and  nitric  acid.  The 
precipitate  so  formed  gradually  dissolves  in  hot  nitric  acid,  and 
from  the  filtered  solution  deposits  on  cooling  in  a  mass  of  homo- 
geneous needles.  Obtained  in  this  way  it  is  pure,  as  testified  by 
the  following  analysis  : 

.  .  Analyses  and  Theory. 


-fAt.  Wgts. 


C     =  19-746 



H    =  1-539 



N    =  23-516 



0    =  21-099 



Ag  =  34-100 



^C-H^N.O-f  AgNOg. 

A  combination  of  the  hypoxanthin  with  silver  was  also  obtained 
by  precipitation  of  its  solution  with  ammoniacal  silver  nitrate ; 



it  contained  6046  per  cent,  silver,  whereas  had  it  been  pure 
C-H^N^OAg^„  it  should  have  contained  61*7  per  cent. 

The  hydrochlorate  of  the  second  base  is  soluble  in  alcohol  but 
precipitated  by  ether ;  on  the  whole  it  is  a  perishable  compound. 
In  one  experiment  Avhere  the  hypoxanthin  had  been  removed 
from  a  mixture  of  the  two  bodies,  this  second  base  was  again 
passed  through  the  phosphomolybdic  process  ;  the  product  gave  a 
precipitate  with  AgXO^  in  the  presence  of  HNO^,  which  proved 
to  be  a  further  quantity  of  hypoxanthin  salt.  Thus  purified 
the  second  base  was  again  passed  through  the  j^hosphomolybdic 
acid  process,  then  converted  into  gold  chloride  salt  and  analysed ; 
it  yielded — 

C  27-37 
H  3-71 
N  11-88 
.    '  O  13-836 

Au  31-864 
CI  11-34 


Computation  of  Analyses. — In  this  compound  the  gold  stands  to 
the  chlorine  as  1  :  2 ;  deducting  now  the  gold  and  chlorine  and 
recalculating  the  percentages,  we  have  : 

Percentages.  —-At.  Wgts.  -^N=1. 

C    =  48-18  4-015  2-7 

H   =    6-53  6-530  4  3 

N   =  20-92  1-494  1-0 

O    =  24-37  1-523  1-0 

=  C3H4NO. 


1.  Leucin  and  Allied  Bodies  ;  Tyrosin. 

The  filtrates  from  the  mercuric  precipitates  were  freed  from 
mercury  by  hydrothion,  and  evaporated  to  a  syrupy  consistence ; 
the  S3TUP  was  treated  with  absolute  alcohol,  and  thereby  separated 
into  a  portion  soluble,  and  another  insoluble,  in  alcohol. 

Portion  Soluble  in  Alcohol. — The  alcohol  was  evaporated,  the 
residue  treated  with  neutral  plumbic  acetate.  The  precipitate 
consisted  mainly  of  j^hosphate  and  chloi'ide,  and  was  removed. 
After  this,  basic  plumbic  acetate  was  added  to  the  filtrate,  and 


the  precipitate  collected  and  decomposed  with  hydrothion  ;  the 
concentrated  filtrate  from  the  plumbic  sulphide  on  treatment  with 
absolute  alcohol  gave  a  crystallisation  of  inosite. 

The  mother-liquor  of  this  inosite,  freed  from  alcohol  by  evapo- 
ration and  acidified,  gave  a  small  precipitate  with  phosphomolybdic 
acid,  thus  proving  that  the  mercuric  acetate  had  not  removed  all 
the  alkaloid,  but  left  some,  which  was  precipitated  by  basic  lead 
acetate  {third  alkaloid). 

The  lead  was  now  removed  from  the  mother-liquor  by  an  excess 
of  sulphuric  acid,  and  the  acid  liquid  extracted  with  large  quan- 
tities of  ether  at  intervals.  The  ethereal  extracts,  after  removal 
of  the  ether  by  distillation,  left  a  mixture  of  acids ;  of  these, 
acetic  acid,  introduced  with  the  mercury  and  lead  salts,  was 
evaporated  on  the  water-bath.  The  remaining  syrup  consisted 
mainly  of  lactic  acid,  but  also  contained  some  succinic  acid,  as  will 
be  described  more  fully  lower  down. 

Portion  Insoluble  in  Alcohol. — This,  on  solution  in  a  minimum 
of  water,  retained  a  quantity  of  solid  matter  in  suspension,  which 
was  separated  by  filtration.  The  residue  on  the  filter  was  pressed, 
and  on  treatment  with  cold  water  gave  to  this  solvent  a  matter 
recognised  as  leucin  and  allied  bodies.  The  matter  insoluble  in  cold, 
but  easily  soluble  in  hot  water,  was  tyrosin. 

The  leucin  was  purified  by  precipitating  the  coloured  impurity 
out  of  its  watery  solution  by  means  of  mercuric  nitrate,  removing 
the  excess  of  mercury  by  hydrothion,  evaporating  the  solution, 
precipitating  the  acid  liquid  by  ammonia,  collecting  and  pressing 
the  precipitate  in  bibulous  paper,-  and  recrystallising  it  from 
spirit.  The  first  crystals  were  pure  leucin  ;  the  second  crystals 
were,  however,  a  different  body,  more  soluble  than  leucin,  and  not 
easily  separated  from  leucin,  on  account  of  the  similarity  of  pro- 
perties.   The  last  mother-liquor  dried  up,  leaving  a  trace  of  matter. 

The  tyrosin  was  purified  by  hydrochloric  acid  and  charcoal, 
and  precipitation  with  ammonia. 

The  mercuric  nitrate  precipitate  from  leucin  was  also  decom- 
posed, and  seemed  to  contain  onl}^  a  small  amount  of  alkaloid 
No.  2. 

Note  on  a  Pecidiar  Potassium  Salt. 

The  liquid  part  of  the  portion  insoluble  in  alcohol  was  diluted 
with  water,  and  treated  with  neutral  lead  acetate ;  the  precipitate, 


decomposed  by  hydrothion,  gave  a  syrup  which,  treated  with 
absolute  alcohol,  deposited  a  peculiar  viscous  colourless  potassium 
salt ;  this  was  isolated,  and,  on  account  of  its  peculiar  nature,  the 
presence  of  the  potassium  was  specially  proved  by  combustion 
and  platinic  chloride.  The  part  of  the  syrup  soluble  in  alcohol 
was  not  further  examined.  The  filtrate  from  the  neutral  lead 
acetate  precipitate  was  treated  with  basic  lead  acetate,  and  the 
new  precipitate  decomposed  with  hydrothion  ;  the  concentrated 
product  was  treated  with  absolute  alcohol,  and  gave  white  inosite, 
partly  anhydrous,  partly  hydrated.  In  the  mother-liquor  of  this 
inosite  nothing,  apparently,  but  some  alkaloid  No.  2  remained, 
The  mother-liquors  from  which  the  foregoing  bodies  had  been  ex- 
tracted and  precipitated  were  freed  from  the  impurities  introduced 
as  reagents  as  far  as  possible  and  evaporated,  and  then  formed  a 
nearly  colourless,  viscid,  uncrystallisable  mass ;  this  was  distilled 
in  superheated  steam,  but  yielded  no  glycerol.  It  gave  a  precipi- 
tate with  phosphomolybdic  acid,  from  which  a  syrupy  alkaloid, 
smelling  hke  sperma,  was  obtained  (alkaloid  No.  3). 




Cholesterin  is  present  in  the  brain  in  very  large  quantity.  In 
the  process  for  the  separation  of  the  brain  principles  above  de- 
scribed it  passes  mainly  into  the  solution  containing  the  kephalins  ; 
these  bodies  have  to  be  precipitated  by  lead ;  myelin  the  same ; 
the  other  phosphatides  have  then  to  be  removed  by  cadmium 
chloride.  At  last  a  mixture  of  cholesterin,  with  several  other 
bodies,  amongst  them  bregenin,  is  obtained  ;  this  mixture  must 
now  be  boiled  with  caustic  potash  in  alcohol,  to  decompose  the 
admixtures,  and  retain  their  decomposition  products  in  solution 
while  cholesterin  crystallises.  It  is  pressed  and  recrystallised  as 
often  as  necessary  to  give  it  its  brilHant  appearance,  and  its 
melting-point,  145°.  It  is  then  the  same  body  as  that  obtained 
from  human  gallstones.  It  crystallises  from  spirit  as  monohydrate, 
C26H44O  +  H2O,  and  loses  the  water  at  100°  or  in  vacuo.  While 
from  spirit  it  crystallises  in  rhombic  plates,  it  is  deposited  from 
chloroform  or  benzol  in  anhydrous  needles.  It  rotates  polarised 
light  to  the  left.  Ether  solution  at  15°:  [a]D  = -3M2° ;  in 
chloroform  solution:  [a]D  =  —36-61°.  It  is  insoluble  in  water, 
little  soluble  in  cold  watery  spirit,  easily  soluble  in  from  5  to  9 
parts  of  boiling  alcohol,  the  more  the  stronger  the  alcohol  is.  It 
can  be  distilled  in  a  vacuum  unchanged  at  a  temperature  of  360^ 
On  distillation  by  heat  under  ordinary  air-pressure  it  is  partly 
transformed  into  hydrocarbons.    It  combines  with  organic  acids 


when  heated  with  them  under  pressure.  When  oxydised  by 
])ermanganate  in  acetic  acid  sohition  it  yields  cholestenic  acid, 
^25-^40^4'  similar  acids  with  5  or  6  atoms  of  oxigen.  AVith 
nitric  acid  it  yields  cholesteric  acid,  Cj._,Hj^O^,  which  is  remark- 
able, as  it  is  also  formed  by  nitric  acid  from  cholic  acid,  and  thus 
it  establishes  a  relationship  between  cholesterin  and  biliary  acids. 
With  bromine  cholesterin  gives  a  product  of  addition,  CggH^OjBrg ; 
with  concentrated  sulphuric  or  phosphoric  acid  it  yields  a  number 
of  hydrocarbons,  cholesterylens,  which  are  isomeric  with  each 

Cholesterin  gives  some  very  characteristic  reactions.  Treated 
with  concentrated  sulphuric  acid  and  a  little  iodine,  it  becomes 
violet,  blue,  green,  and  red  in  succession.  This  reaction  is  useful 
for  recognising  cholesterin  under  the  microscope.  When  a  little 
cholesterin  is  evaporated  with  a  drop  of  nitric  acid  at  a  gentle 
heat,  a  yellow  spot  remains,  which,  if  covered  while  warm  with  a 
drop  of  ammonia,  becomes  red  ;  this  red  is  not  altered  by  the 
addition  of  fixed  alkali. 

Reaction  of  Cholesterin  with  Oil  of  Vitriol  and  Chloroform  ;  Spectral 
Phenomena  of  the  Product. 

The  cholesterin  was  obtained  from  the  brain,  and  fused  at 
147°  C.  A  portion  was  dissolved  in  chloroform,  and  an  equal 
bulk  of  oil  of  vitriol  added  ;  this  produced  a  dark  red  coloration 
both  in  the  chloroform  and  in  the  acid. 

The  chloroform  solution  thus  obtained  presented  the  following 
spectra  : 

The  most  concentrated  solution  obscured  all  but  the  red. 

After  it  had  been  a  little  more  diluted  one  broad  band  appeared 
in  yellow  and  green,  and  another  in  green  to  blue,  but  it  had  only 
about  half  the  intensity  of  the  other. 

AVhen  it  was  still  more  diluted  the  broad  band  split  into  two 
bands,  the  band  in  green  to  blue  remaining. 

The  solution  when  poured  into  a  dish  became  rapidly  blue, 
green,  and  at  last  colourless. 

On  evaporation  to  dryness  and  re-addition  of  sulphuric  acid  to 
the  residue,  a  sHght  restoration  of  a  dirty  red  colour  took  place, 
but  with  chloroform  no  restoration ;  the  permanent  colour  of  the 
residue  was  a  light  green. 

Reaction  of  Cholesterin  ivith  (Til  of  Vitriol  and  Glacial  Acetic  Acid. 

The  dark  red-brown  oil  of  vitriol  solution  of  cholesterin  when 
thrown  into  glacial  acetic  acid  dissolves  entirely  to  a  dark  red 
solution  almost  impenetrable  to  light.  This  solution  presents 
the  following  spectra  : 

Through  the  concentrated  liquid  only  red  passes  ;  when  it  is 
more  diluted  two  bands  appear,  one  feeble,  in  red,  the  other 
strong,  in  orange  and  yellow. 

In  the  still  more  diluted  liquid  three  bands  appear,  the  solution 
being  brilliant ;  the  third  band  is  broad,  and  reaches  to  F. 

Hence  the  middle  band  of  the  chloroform  solution  was  absent 
from  this  ;  the  broad  band  of  the  chloroform  solution  was  there, 
but  much  stronger  and  broader.  There  was  a  powerful  green 
fluorescence.  As  the  third  band  of  the  acetic  acid  solution  is  new 
and  does  not  occur  in  the  chloroform  solution,  at  least  two  coloured 
bodies  are  produced  in  this  reaction. 

By  oxidation  with  chromic  acid  in  acetic  acid,  cholesterin  yields 
an  acid  of  the  formula  0^4113^^05,  and  other  products. 

Phytosterin,  the  cholesterin  of  plants,  is  the  second  isomer, 
C2gH440  +  H20;  its  fusing-point  is  132°  to  133^;  its  chloroform 
solution  turns  to  the  left  =[a]D  =  —34-2°. 

Isocholesterin,  OggH^^O  is  the  third  isomer,  and  occurs  in  the  wool- 
fat  from  sheep,  together  with  the  ordinary  cholesterin.  When 
crystallising  from  alcohol  it  forms  gelatinous  masses  ;  from  ether 
it  crystallises  in  needles.  It  does  not  give  the  reaction  with  oil 
of  vitriol  and  chloroform  which  cholesterin  gives.  It  fuses  at  137° 
to  138°. 

Paracholesterin,  O^gH^^O  +  HoO,  is  the  fourth  isomer,  and  is 
obtained  from  the  fungus  sethalium  flavum.  Fuses  at  134°  to 
134 '5°.  It  differs  from  phytosterin  only  by  its  rotation  being 
less,  namely  [a]D=  —  28'88°. 

The  quantation  of  cholesterin  in  the  brain  is  connected  with 
many  difficulties.  It  is  not  impossible  that  the  bearing  of  cho- 
lesterin with  benzoic  acid  under  pressure  at  high  temperature, 
200°,  may  be  utilised  for  this  purpose.  The  two  bodies  combine 
and  form  an  ether,  which  is  almost  insoluble  in  boiling  spirit ;  but 
crystallises  from  ether  in  peculiar  rectangular  plates.  The  benzoate 
of  isocholesterin  crystallises  in  needles.  When  such  plates  and 
needles  are  obtained  mixed,  they  can  be  separated  by  levigation 


with  spirit.  This  process  therefore  offers  a  means  of  separating 
cholesterin  from  isocholesterin,  when  they  occur  mixed  with  each 
other,  as  they  do  in  wool-fat.  It  may  possibly  serve  in  some  cases 
of  brain  analysis,  and  for  this  purpose  the  reaction  should  be 
borne  in  mind. 



Inosite  occurs  in  the  parenchyma  of  most  tissues  of  the  animal 
body,  but  in  largest  quantity  in  muscle  and  the  brain.  It  also 
occurs  in  plants,  e.g.  in  beans,  and  in  Sauterne  wine.  It  crystal- 
lises as  a  dihydrate,  CgHj^Og -f- 2H2O,  and  does  not  rotate  the 
ray  of  polarised  light.  It  does  not  undergo  the  alcoholic,  but 
easily  the  lactic  fermentation,  and  the  lactic  acid  which  results 
is  optically  inactive.  With  nitric  acid  it  yields  a  trinitrited, 
and  a  hexanitrited  substitution  compound,  CgHg(N02)30g,  and 
CgHg(NOo)gO(3.  Inosite  is  completely  precipitated  from  its  solu- 
tion by  basic  lead  acetate  ;  the  lead  compound  is  decomposed  by 
hydro thion,  and  the  solution  evaporated  to  a  small  bulk.  AVhen 
toHhis  alcohol  is  added,  crystals  of  inosite  are  formed  on  standing. 
The  following  is  a  good  test  for  inosite.  Evaporate  the  liquid  to 
be  tested  for  inosite  in  a  porcelain  dish  to  the  bulk  of  a  few  drops, 
and  then  add  a  small  drop  of  mercuric  nitrate.  This  produces  a 
yellowish  precipitate.  When  this  is  spread  as  far  as  possible  over 
the  surface  of  the  porcelain,  and  the  dish  is  further  heated  with 
great  caution,  there  remains,  as  soon  as  all  fluid  is  evaporated,  and 
provided  that  no  excess  of  reagent  has  been  added,  a  residue 
w^hich  is  whitish-yellow  at  first,  but  soon  becomes  more  or  less 
dark  red,  according  to  the  quantity  of  inosite  present.  The 
colour  disappears  when  the  dish  gets  cold,  but  reappears  on  re- 
heating it  gently.  If,  when  the  colour  has  appeared,  the  dish  is 
overheated  in  the  slightest  degree,  the  mixture  undergoes  a  sudden 
decomposition,  though  without  incandescence,  and  becomes  black. 
Inosite  is  not  capable  of  reducing  Fehling's  solution.  Its  bearing 
with  copper  salts  was  little  understood  before  the  following  obser- 
vations on  the  subject  were  made. 

Compound  of  Cerebral  Inosite  with  Cupic  Oxide. — When  to  a  hot 
solution  of  inosite  (from  ox-brain)  a  saturated  solution  of  copper 
acetate  is  added,  a  light  green  precipitate  immediately  ensues. 


When  copper  acetate  is  added  in  excess,  so  that  the  filtrate  has  a 
blue  colour,  and  the  mixture  is  warmed,  almost  all  inosite  is  pre- 
cipitated out  of  the  solution.  The  green  precipitate  of  inosite 
copper  can  be  heated  with  pure  water,  without  more  than  traces 
of  copper  dissolving  in  the  water.  The  solution  is  colourless,  but 
gives  a  brown  coloration  with  potassium  ferrocyanide  and  acetic 
acid.  The  light  green  precipitate  of  inosite  copper  {first  precij)i- 
tate)  on  being  dried  in  the  air-bath  at  110°,  became  dark  green, 
nearly  black,  and  was  then  analysed.  It  contained  47*11  per 
cent,  of  Cu. 

A  compound  of  one  molecle  of  inosite  with  three  molecles  of 
cupric  oxide,  CgH^^^^d  +  3CuO,  of  which  the  atomic  weight  would 
be  182  +  238-2  =  420-2,  requires  45-2  per  cent. 

The  compound  when  hoUed  with  water  is  decomposed  at  the  place 
where  the  vessel,  whether  platinum  or  glass,  is  hottest.  It  is  not  de- 
composed when  warmed  gently  on  the  water-bath .  When  a  solution 
of  inosite  is  evaimxited  with  excess  of  coj)per  acetate  on  the  water- 
bath,  all  inosite  becomes  insoluble  in  the  shape  of  the  compound 
described  in  the  foregoing.  The  excess  of  acetate  may  be  washed 
out  with  warm  water,  but  the  precipitate  may  not  be  boiled  in 
platinum  or  glass  over  the  free  flame,  as  it  forms  a  reddish-brown 
adherent  decomposition  product.  The  compound  is  soluble  in 
acetic  acid,  with  slight  coloration,  without  residue.  It  is  soluble 
in  ammonia,  with  a  deep  blue  colour.  A  trace  of  matter  remains 
insoluble  (which  is  not  the  case  with  the  acetic  acid)  and  may 
explain  the  slight  excess  of  copper  found  in  the  analysis. 

When  this  compound  was  heated  on  platinum,  it  showed  the 
following  remarkable  bearing  :  it  scintillated  and  deflagrated, 
while  evolving  acid  fumes.  A  red  residue  was  left,  which  on 
being  thrown  into  the  air  took  fire  and  burnt  (pyrophorus) .  Pro- 
bably the  three  molecles  of  cupric  oxide  gave  up  half  their  oxigen, 
and  remained  as  cuprous  oxide  mixed  with  some  carbonaceous 

Second  Precipitate. — On  addition  of  more  copper  acetate  to  the 
solution  from  which  the  first  precipitate  had  been  filtered,  and 
application  of  a  gentle  heat,  a  second  precipitate  ensued,  which 
was  and  remained  green.  Dried  at  110°  it  gave  on  analysis,  mean 
of  three  quantations,  44-59  per  cent.  Cu. 

When  this  compound  in  the  state  of  powder  was  heated  at  the 
margin,  it  took  fire,  and  then  burned  spontaneously  through, 


leaving  a  red  residue.  This  residue  also  was  pyrophoroiis  when 
thrown  into  the  air. 

Third  Precipitate. — The  mother-liquor  of  the  second  precipitate 
was  concentrated  by  evaporation,  and  formed  a  third  precipitate. 
This,  after  isolation,  was  dissolved  in  dilute  ammonia,  and  repre- 
cipitated  by  gentle  eva2)oration.  It  was  light  green,  and  when 
gently  dried  was  analysed,  and  found  to  contain  40"  10  per  cent. 
Cu.  " 

A  trihydrate  of  the  cupric  inosite  requires  40-10  per  cent,  of  Cu. 
That  this  compound,  CgHj2^6  +  ^^^^  +  2^^20  (atom,  weight 
=  474-2)  had  really  been  obtained,  was  further  proved  by  the 
loss  which  it  suffered  on  being  dried  at  110°,  being  equal  to  three 
molecles  of  water.  For  the  dry  compound  gave  on  analysis 
45-38  per  cent.  Cu,  while  theory  requires  45-2  per  cent.  Cu. 

Fourth  Precipitate. — This  was  obtained  after  the  third,  by  the 
same  process  as  the  latter.  It  was  bright  green,  and  dried  at  100° 
gave  on  analysis  45-68  per  cent.  Cu. 

The  inosite  from  ox-brain  used  in  the  foregoing  research  was  a 
finely  crystallised,  on  the  whole  very  pure  specimen.  Nevertheless, 
the  first  precipitate  was  somewhat  impure,  as  indicated  by  its 
2)hysical  properties  and  its  composition.  But  the  precipitates 
Nos.  3,  4,  were  so  pure  that  their  analyses  yielded  almost  theo- 
retical results. 

It  was  therefore  very  surprising  that  an  equally  well  crystallised 
and  apparently  perfectly  pure  specimen  of  inosite  from  human  brain, 
on  being  mixed  and  treated  with  copper  acetate  like  the  inosite 
from  ox-brain,  should  yield  totally  different  and  greatly  varying 

The  first  p}recipitate,  dried  in  vacuo  over  sulphuric  acid,  lost 
at  110°  1-53  per  cent.  H^O,  and  contained  47*48  per  cent.  Cu. 

The  second  precipitate,  dried  in  vacuo,  etc.,  lost  at  110°  1*77  per 
cent.  H.,0,  and  contained  51-23  per  cent.  Cu. 

The  mixture,  on  further  evaportion,  formed  a  third,  and  after 
its  removal  only  an  insignificant  fourth  precipitate,  although  after 
addition  of  copper  solution  it  formed  a  fifth  and  a  sixth  precipi- 
tate, which  contained  more  copper  than  the  first  precipitate. 

The  third  precipitate,  dried  in  vacuo  over  oil  of  vitriol,  lost  at 
110°  2*85  per  cent.  H._,0,  and  contained  47*73  per  cent.  Cu. 

The  fifth  and  sixth  ptrecipitates,  dried  in  vacuo  over  sulphuric 
acid,  lost  at  110°  1*34  per  cent.  H^,  and  contained  49*81  per 
cent.  Cu. 


These  precipitates,  therefore,  contained  about  two,  or  four,  or 
six  per  cent,  more  copper  than  corresponds  to  tricupric  inosite. 
When  they  were  dissolved  in  ammonia  and  the  solution  evapo- 
rated cautiously,  discoloured  products  were  obtained.  From 
these  data  I  conclude  that  the  inosite  from  the  human  brain  is 
either  altogether  different  from  that  contained  in  the  brain  of  the 
ox,  or  is  accompanied  by  another  similar  carbohydrate  of  less 
stable  quality.  In  any  case,  the  subject  calls  for  further  investi- 

Inosite  is  a  hexadynamic  alcohol,  and  forms,  as  we  have  seen 
above,  two  nitrite  ethers,  a  hexanitrite  and  a  trinitrite.  Similarly, 
though  probably  not  by  substitution  of  hydrogen,  it  forms  a 
tricupric  compound ;  and  perhaps  at  the  same  time  a  small  quan- 
tity of  a  hexacupric  one,  if  the  compounds  with  more  than  45*2 
per  cent.  Cu  have  not  to  be  considered  as  combinations  with 
bodies  other  than  inosite. 


1.  Lactic  Acid. 

The  mixed  acids  were  heated  on  the  water-bath  until  acetic 
acid  was  expelled,  redis  solved  in  water,  and  neutralised  while  hot 
with  freshly  prepared  zinc  carbonate.  The  zinc  salt  was  crystallised 
and  recrystallised  an  indefinite  number  of  times,  until  perfectly 
white,  crystallised  throughout,  and  homogeneous.  During  these 
operations  a  coloured  matter  became  insoluble,  and  had  to  be 
removed  by  repeated  filtration.  The  crystallised  salt  was  found 
to  be  pure  zinc  lactate,  containing  the  variety  of  lactic  acid  known 
as  lactic  acid  from  flesh,  or  sarkolactic  acid.  Not  only  did  the  salts 
yield  the  particular  amount  of  water  of  crystallisation  which  dis- 
tinguishes them  from  the  zinc  salts  of  the  fermentation  lactic 
acid,  but  the  free  acid  itself  showed  the  power  of  polarising  light, 
which  is  not  possessed  by  the  product  of  the  fermentation  of 

Summanj  of  Analyses  of  Zinc  Lactate  from  Human  Brain. 

The  salt  was  dried  in  vacuo  until  it  lost  no  longer  in  weight, 
and  then  at  110°  until  constant.   Two  specimens  showed  a  loss  of 
water  of  crystallisation  amounting  to  12-82  per  cent.,  and  12*90 
per  cent.    This  corresponds  to  the  theory  of  12*82  per  cent. 
water  of  crystallisation. 


In  the  same  hydrated  salt,  dried  in  vacuo,  the  zinc  was  estimated 
by  precipitation  with  carbonate  in  the  usual  manner,  and  found 
in  two  experiments  to  amount  to  23-24  per  cent,,  and  23 "28  per 
cent.  ;  while  theory  requires  23-35  per  cent.  Zn. 

Summanj  of  Analyses  of  Zinc  Lactate  from  Ox  Brain. 

.  The  salt,  after  having  been  dried  in  vacuo  over  oil  of  vitriol, 
lost  12-80  per  cent.  HoO  at  110°. 

The  zinc  was  estimated  in  the  anhydrous  salt  by  precipitation 
and  ignition,  and  found  in  two  experiments  to  amount  to  26*69 
j)er  cent.,  and  26-69  per  cent.  Theory  requires  26-79  per  cent. 
Zn  in  the  anhydrous  salt,  CgHj^O^Zn.  The  formula  of  the 
hydrated  salt  is  Zn{C^B.Jd.^.^{^, 

Physical  Peculiarities  of  the  Lactic  Acid  from  Brain  and  its  Zinc  Salt. 

When  the  lactic  acid  as  obtained  from  the  ether  extract,  a  state 
in  which  it  was  yet  yellowish  and  gave  out  an  odour,  was  de- 
colorised by  animal  charcoal,  and  a  somewhat  concentrated 
solution  of  it  was  placed  in  a  tube,  of  220  mm.  in  length,  and 
containing  about  26  cc.  of  fluid,  and  subjected  to  the  influence  of 
the  polarised  ray  of  yellow  light  in  a  Wild's  polaristrobometer,  it 
was  found  to  turn  the  plane  of  polarisation  to  the  left  (to  the 
measured  extent,  in  the  particular  instance  of  an  acid  of  uncertain 
strength,  of  V  20'). 

The  acid  was  next  transformed  into  zinc  salt  by  boiling  with 
zinc  oxide,  and  the  solution  of  salt  was  evaporated  to  the  same 
volume  as  that  occupied  by  the  free  acid.  It  now  turned  the 
plane  of  polarisation  still  to  the  left,  but  to  the  extent  of  3°  15'. 
Thus  the  rotation  from  0  to  the  left  had  been  much  increased, 
more  than  doubled,  by  the  introduction  of  the  zinc  and  the 
attendant  thermal  and  hydric  operations. 

The  zinc  salt,  which  had  been  obtained  in  a  state  of  purity,  as 
proved  in  the  previous  j^aragraph,  was  dissolved  in  water  and 
decomposed  with  hydrothion  ;  the  free  acid  was  concentrated  and 
became  a  colourless  syrupy  liquid ;  in  this  state  it  was  not  per- 
fectly brilliant,  but  had  a  slight  haze,  probably  from  a  trace  of 
finely  divided  sulphur.  It  was  therefore  allowed  to  stand  for 
two  months  in  a  quiet  place,  and  when  the  trace  of  particles  had 
completely  deposited,  the  clear  part  was  isolated  by  decanta- 


This  acid,  on  being  placed  in  a  tube  of  100  mm.  in  length  into 
the  polaristrobometer,  now  turned  the  plane  of  polarisation  to  the 
right,  in  the  particular  instance  of  an  acid  of  uncertain  concentra- 
tion, to  the  extent  of  2°  17'  (average  of  seven  observations). 

I  have  made  no  attempt  to  determine  the  specific  rotating-power 
of  the  lactic-acid  from  the  brain.  The  reason  for  this  is  the  circum- 
stance first  observed  by  Wislicenus,  that  the  rotating-power  of  sar- 
kolactic  acid  changes  under  a  great  number  of  influences,  such  as 
heat,  water,  and  time.  Thus  free  sarkolactic  acid,  when  dried  over 
sulphuric  acid  in  vacuo  during  21  months,  is  transformed  into  a 
mixture  of  lactic  acid,  CgHgO^  (16-50  per  cent.);  anhydride, 
C^HioOg  (84-19  per  cent.) ;  and  lactide,  CgH^O^  (16-04  per  cent). 
The  solution  of  this  mixture  turns  the  plane  of  polarised  light  to 
the  left  (ft)=  -85*93°.  It  is  probable  that  all  three  products 
on  treatment  with  water  are  transformed  back  into  sarkolactic 

The  watery  solution  of  sarkolactic  acid  as  ordinarily  obtained, 
directly  after  extraction  and  concentration,  shows  a  considerable 
polarisation  to  the  left.  This  power  is  suddenly  and  greatly 
diminished  after  every  addition  of  water  or  spirit,  but  on  stand- 
ing it  rises  again,  without,  however,  reaching  its  former  value. 
The  diminution  of  specific  rotatory  power  by  dilution  is  the 
greater,  the  more  concentrated  was  the  solution  used  for  dilution, 
that  is  to  say,  the  greater  was  the  dilution  in  proportion  to  the 
strength  of  the  original  solution.  These  changes  are  due  to  the 
presence  of  anhydrides  and  lactide.  And  as  every  preparation  of 
sarkolactic  acid  contains  these  anhydrides,  according  to  Wisli- 
cenus, pure  sarkolactic  acid,  as  a  preparation,  does  not  exist,  and 
therefore  its  specific  rotatory  power,  which  this  author  surmised 
to  be  to  the  right,  cannot  be  accurately  determined. 

I  have  shown  above  that  pure  sarkolactic  acid  prepared  from 
the  zinc  salt  turns  the  plane  of  polarised  light  freely  to  the  right. 
But  the  solution  of  the  zinc  salt  from  which  this  acid  was  pro- 
duced turned  energetically  to  the  left.  The  saturated  normal 
solution  of  zinc  salt  turns  the  plane  of  polarised  light  steadily 
7°  7'  to  the  left.  In  over-saturated  solutions  the  turning  faculty 
is  not  increased,  as  might  be  supposed,  but,  on  the  contrary,  is 

The  polarising  faculties  of  sarkolactic  acid,  its  hydrate,  zinc 
salt,  and  anhydride  may  be  described  as  follows  : 


Turning  farthest  to  the  right  -  C3Hg03. 

Turning  less  far  to  the  right  -  CgHgOg  +  H2O. 

Turning  least  to  the  left    -  -  2(C3H503)Zn. 

Turning  more  to  the /^/Z  -  -  2(C3H5()3)Zn  +  2H,0. 

Turning  farthest  to  the  left  -  CgHjoO^. 

Peculiarities  of  the  Calcium  Salt  of  Lactic  Acid  from  Hmian 


This  salt  was  made  from  pure  lactic  acid  obtained  as  above  de- 
scribed. Its  solubility  in  water  was  so  great  that  attempts  at  its 
crystallisation  from  this  solvent  were  foiled  by  the  solution  setting 
to  a  solid  mass.  It  was  consequently  recrystallised  from  strong 
spirit.  When  dried  in  air,  it  was  a  light  voluminous  spongy  mass 
of  crystals,  which  on  being  dried  at  105°  lost  21-2  per  cent,  of 
water  of  crystallisation,  and  contained  14-14  per  cent,  of  Ca. 

These  data  do  not  correspond  to  any  of  the  recorded  data  con- 
cerning this  salt,  which  recorded  data  themselves  differ  from  each 
other,  or,  on  the  assumption  that  there  was  only  one  hydrate, 
contradict  each  other.  It  is  noAv  assumed  by  some  that  the  sarko- 
lactate  of  calcium,  as  commonly  obtained,  has  the  formula — 

,   2Ca,4(C3H^03)  +  9H2O    -       -       water  =  27 '09  per  cent. 
Formerly,  however,  a  hydrate  was  mostly 

described  as  containing  water  -       -  =  24*83  per  cent. 

The  hydrate  just  described  contains  water  21*2  percent. 

Now,  the  second  salt  corresponds  to  one  with  4  molecles  of 
water  of  crystallisation,  while  the  last  leads  to  no  even  proportion 
between  salt  and  water  of  crystallisation,  but  is  intermediate  be- 
tween the  salt  containing  4  molecles  and  a  hypothetical  salt 
containing  3  molecles  of  water,  which  requires  19-89  per  cent. 

The  new  salt  must  therefore  be  considered  either  as  a  compound 
or  mixture  in  nearly  molecular  pro2)ortion  of  the  salt,  containing 
24-83  per  cent.,  with  the  hypothetical  salt  containing  19*89  per 
cent,  of  water,  or,  in  more  simple  terms,  as  a  salt  consisting  of 
2  molecles  of  anhydrous  lactate  and  7  molecles  of  water  of  crys- 
tallisation, requiring  22*35  per  cent.  H^O ;  possibl}^  a  lower 
homologue  of  the  salt  with  9  molecles  of  water.  The  dej^ression 
of  the  water  by  mere  admixture  of  anhydride  was  improbable, 
owing  to  the  uniform  character  of  the  crystallisation. 

I  am,  therefore,  of  opinion  that  there  are  at  least  three,  if  not 
four,  different  crystallised  hydrates  of  calcic  lactate,  and  that  the 


amount  of  hydration  is  probably  dependent  upon  the  concentra- 
tion of  the  sohition  if  it  be  a  watery  one,  or  upon  the  aquosity  of 
the  solvent  if  it  be  spirit. 

The  preparations  of  lactic  acid  from  the  brain  of  man  and  the 
ox,  which  I  have  described  above,  leave  no  room  for  doubt  regard- 
ing their  nature  ;  they  are  specimens  of  the  one  optically  active 
sarkolactic  acid,  yielding  the  precisely  characteristic  zinc  salt ; 
that  they  did  not  yield  the  ordinary  calcium  salt  is  of  little  con- 
sequence, as  the  question  of  the  composition  of  the  calcium  salts 
of  sarkolactic  acid  is  not  exhaustively  answered.  Whatever  may 
be  the  issue  of  the  discussion  regarding  the  constitution  of  the 
different  lactic  acids,  the  facts  now  ascertained  regarding  cerebral 
lactic  acid  cannot  thereby  be  affected. 

I  have  disposed  of  some  opinions  regarding  the  alleged  presence 
of  a  second  acid  in  sarkolactic  acid  already  in  1877  (compare  my 
^  Pathology  of  the  Urine,'  1877,  p.  461  et  seq.).  I  now  prove  for 
the  brain,  what  Erlenmeyer  has  proved  for  the  flesh,  namely,  that 
it  contains  only  one  lactic  acid. 

2.  Formic  Acid. 

The  acids  extracted  by  ether  after  precipitation  of  the  alkaloids 
were  in  one  experiment  placed  in  a  retort,  and  subjected  to  dis- 
tillation. The  main  part  of  the  distillate  consisted  necessarily  of 
acetic  acid.  The  acids  were  neutralised  by  barium  carbonate 
and  evaporated  to  crystallisation;  the  first  crystals  gave  53-09 
per  cent.  Ba  (acetate  requires  53-72  per  cent.  Ba) ;  the  second 
crystals  gave  55*53  per  cent.  Ba,  -and  gave  a  strong  formiate 
reaction  with  nitrate  of  mercurous  oxide.  It  is,  therefore,  pro- 
bable that  the  water  extract  of  the  brain  contains  a  small  amount 
of  formic  acid,  as  has  already  been  stated  by  Von  Bibra  and 
Mtiller.  The  amount  was,  perhaps,  not  greater  than  that  of 
succinic  acid,  to  be  described. 

3.  Succinic  Acid. 

{a)  In  Ox-brain. — The  mother-liquors  of  the  zinc  lactate  gave 
with  ferric  chloride,  not  in  the  cold,  but  on  boiling,  a  rust-coloured 
precipitate,  soluble  in  excess  of  chloride,  forming  a  dark-red  solu- 
tion. The  united  mother-liquors  were  cautiously  precipitated 
while  boiHng,  and  the  compound  filtered  off.  They  were  next 
boiled  with  barium  carbonate,  and  the  precipitate  filtered  off". 



The  latter  was  extracted  with  hot  dilute  acetic  acid,  in  which 
the  ferric  precipitate  was  insoluble.  The  ferric  precipitates  were 
dissolved  in  water,  and  HoSO^,  and  extracted  with  ether;  the 
ether  solution  left  the  acid  free. 

The  acid,  easily  soluble  in  water,  crystallised  on  evaporation, 
fused,  and  sublimed  in  white  vapours.  The  vapours  had  a  pun- 
gent smell,  and  formed  white  crystals  on  condensation.  The 
acid  was  entirely  volatilised  without  leaving  any  charcoal. 

The  sublimated  crystals  dissolved  in  water,  and  gave  a  clear 
and  colourless  solution.  This  was  cautiously  neutralised  by  sodic 
carbonate.  The  solution  gave  a  rusty  jorecipitate  with  ferric 
chloride,  soluble  in  excess  of  chloride.  It  gave  a  white  precipitate 
with  mercurous  nitrate,  not  altered  by  boiling ;  gold  chloride  gave 
no  reaction,  which  excludes  malonic  acid  ;  uranic  nitrate  gave  no 
reaction.  After  boiling  and  concentration  the  solution  of  the 
sodium  salt  gave  a  precipitate  with  BaCl^.  This  was  soluble  in 
HNO.3,  and  reprecipitated  by  NH^HO  ;  still  more  by  a  little  spirit. 

This  acid  is  consequently  siccclnic,  O^HgO^. 

(b)  In  the  Human  Brain. — The  process  described  in  the  fore- 
going regarding  the  brain  of  the  ox  was  repeated  on  the  mother- 
liquor  of  zinc  lactate  from  the  brain  of  man,  and  exactly  identical 
results  were  obtained.  The  ferric  salt  was  decomposed  and  the 
acid  extracted  by  ether.  It  remained  in  a  crystalline  state,  and 
was  sublimed.  The  reactions  were  then  made  upon  the  sublimate, 
and  found  to  agree  exactly  with  those  of  succinic  acid. 

This  experiment  was  repeated  on  a  second  quantity  with  iden- 
tical results. 

Succinic  acid  is  thus  shown  to  be  a  normal  ingredient  in  small 
quantity  of  the  brain  of  man  and  of  the  ox.  Miiller,  when  extract- 
ing lactic  acid  from  brain,  had  searched  for  succinic,  but  had  not 
obtained  any.  This  is  explicable  on  several  grounds  :  firstly,  his 
method  was  not  calculated  to  obtain  it  (he  waited  for  crystals  to 
form  in  the  concentrated  lactic  acid) ;  and,  secondly,  the  quan- 
tities of  brain-matter  employed  by  him  were  probabl}^  too  small. 

The  significance  of  succinic  acid  in  nerve-marrow  is  probably 
connected  with  that  of  the  disintegration  of  the  albuminous  sub- 
stances. But  the  possibility  of  merely  accidental  presence  must 
not  be  lost  sight  of,  as  succinic  acid  is  present  in  many  kinds  and 
parts  of  vegetables  used  for  food  by  man  and  animals,  and  in 
v/ine  and  other  fermented  liquids,  in  which  it  is  produced  by  fer- 
mentation from  sugar. 




The  brain  as  a  whole  is  an  aggregated  mass  of  bioplasm,  which 
derives  its  peculiarity  mainly  from  specific  chemical  additions. 
The  latter  have  been  treated  of  in  the  earlier  parts  of  this  treatise, 
and  there  remain  for  consideration  the  albuminous  substances 
which  constitute  the  stroma  of  the  bioplasm,  in  which  the  specific 
matters  are  distributed,  or  with  which  they  are  combined  in  such 
a  manner  as  to  produce  the  living  brain-tissue  or  neuroplasm. 
It  is  naturally  deposited  in  the  shape  of  cells  and  fihres,  the  cells 
being  termed  ganglionic,  because  they  were  first  observed  in 
nerve-ganglia,  anatomically  so-called.    The  fibres  contain  more 
of  the  specific  principles  than  the  cells,  but  after  they  are  de- 
ducted, the  albuminous  principles  in  cells  and  fibres  are  very 
much  alike.    By  analytical  means  some  part  of  each  of  the  prin- 
ciples can  be  extracted  and  identified,  but  it  is  as  yet  impossible 
to  separate  the  whole  of  them  from  each  other  unchanged.    It  is 
found,  principally  by  the  method  of  extraction  of  the  comminuted 
tissue  by  means  of  salt  water  of  varying  concentration,  that 
neuroplasm  contains  small  quantities  of  soluble  albumen,  partly 
exhibiting  the  properties  of  serum  albumen  ;  small  quantities  of 
fibrin,  and  considerable  quantities  of  what,  from  its  similarity  to 
the  body  forming  the  stroma  of  the  blood-corpuscles,  has  been 
termed  globulin,  but  which  by  its  function  is  characterised  as  a 
plastin.    And  in  order  not  to  assume  that  the  plastin  of  the  nerves 
is  identical  in  every  respect  with  the  plastin  of  other  organs,  I 
propose  to  treat  of  it  as  neiiroplastin.    In  the  process  of  extraction 
of  the  five  groups  of  constituents  of  the'  brain,  the  albuminous 
matters  all  become  insoluble,  and  change  their  reactions  with 
those   agents   in  which  they  were  previously  soluble.  The 
coagulated  mass  of  brain-tissue  after  exhaustion  with  alcohol  is 



thus  a  mixture  of  curdled  albumen,  and  of  fibrin  and  neuroplastin 
changed  by  heat  and  the  influence  of  alcohol.  It  contains,  further, 
all  the  cytophosphatides  from  the  nuclei  of  the  nerve-cells,  and 
from  the  sheaths  of  the  nerve-fibres  ;  the  material  of  these  sheaths 
themselves,  which  is  probably  analogous  in  composition  to  that 
of  the  sheaths  of  the  muscular  fibres  ;  and  the  tissue  of  the 
capillaries,  which  pervade  the  brain-tissue.  But  neuroplastin  is 
by  far  the  greater  portion  of  the  insoluble  residue,  and  albumen 
and  fibrin  do  probably  not  amount  to  one-eighth  of  the  weight  of 
the  neuroplastin.  The  total  weight  of  the  albuminous  matters  of 
the  human  brain,  free  from  its  membranes,  amounts  to  7*0  per 
cent,  at  least;  in  some  parts  it  is  7 '6  per  cent.,  and  may  vary  be- 
tween these  figures  in  different  parts.  Grey  neuroplasm  contains 
7 '6  per  cent.,  white  tissue  8*6  per  cent.  This. is  not  quite  equal 
to  half  the  solids  in  grey  neuroplasm,  which  amount  to  about 
15  per  cent.,  while  in  white  neuroplasm  the  amount  of  solids 
rises  much  higher.  The  specific  ingredients  of  white  neuroplasm 
may  amount  to  19*16  per  cent.,  and  if  8  "6  per  cent  albuminous 
matters  are  added  to  this,  we  have  a  total  of  27*76  per  cent,  of 
solids,  to  which  some  salts  have  yet  to  be  added.  It  is  therefore 
not  surprising  that  some  specimens  of  white  neuroplasm  should 
yield  as  much  as  30  per  cent,  of  solids.  The  albuminous  matters 
have  sometimes  been  found  as  high  as  10  per  cent.,  but  it  is 
doubtful  how  far  in  these  cases  they  were  fully  extracted  with 
alcohol.  As  much  valuable  information  regarding  the  albuminous 
substances  in  general  had  been  obtained  by  chemolysis,  even  in 
cases  where  the  substances  could  not  be  obtained  in  a  pure  state, 
I  applied  the  process  to  neuroplastin  in  the  first  instance  with  the 
following  results  : 

Chemolysis  hy  Barita  of  Neuroplastin  from  Brain. 

The  albuminous  matter  was  obtained  by  exhausting  brain 
(human  or  ox)  with  spirit  of  85  per  cent,  strength. 

An  amount  of  neuroplastin  about  100  g.  in  weight,  with  six 
times  its  weight  of  crystallised  barita  and  four  times  its  weight 
of  water  (part  of  the  water  being  used  to  soak  the  albumen  for 
some  time  previous  to  the  admixture  of  the  barita),  was  taken  for 
the  chemolysis. 

The  apparatus  employed  was  an  autoclave  of  wrought-iron,  and 
holding  about  5  litres.    The  cover  was  air-tight  and  secured  by  a 



screw  clamp,  while  an  adjustable  valve  provided  for  the  escape  of 
gas  in  case  of  the  pressure  rising  beyond  certain  limits.  The 
mixture  above  described  was  placed  in  the  chemolyser,  and  the 
temperature  raised  to  180°  0.  hy  means  of  a  gas-burner  placed 
underneath.  The  heat  was  maintained  at  this  height  for  six 
hours,  whereupon  the  chemolyser  was  allowed  to  cool.  When 
the  autoclave  was  opened,  its  contents  emitted  a  strong  smell  due 
to  ammonia,  compound  ammonias,  albuminol,  and  other  products 
of  decomposition. 

The  semi-solid  mass  was  extracted,  placed  in  a  platinum-still 
with  much  water,  and  subjected  to  distillation.  Two  litres  of 
distillate  were  drawn  off,  containing  ammonia  and  compound 
ammonias  in  solution,  and  albuminol  in  small  white  flakes  ;  the 
latter  were  removed  by  extraction  with  ether. 

The  ether  solution  on  evaporation  left  a  small  residue  consisting 
of  albuminol  mixed  with  a  peculiarly  smelling,  probably  sulphurised 
tody;  the  latter  was  gradually  volatilised  on  standing,  leaving  the 
albuminol,  which  crystallised. 

The  watery  distillate  was  neutralised  with  hydrochloric  acid  and 
evaporated  to  dryness,  and  the  mixture  of  salts  was  further 
treated  for  the  separation  of  compound  ammonias  from  simple 
ammonia,  as  will  be  described  below. 

The  mixture  from  which  the  volatile  alkalies  had  been  distilled 
was  filtered,  and  the  insoluble  matter  isolated. 

This  insoluble  maUer  was  treated  with  water,  ether,  and  hydro- 
chloric acid.  A  small  quantity  of  a  fatty  acid  went  into  solution 
in  the  ether,  barita  with  phosphoric  and  oxalic  acid  dissolved  in 
the  acid  water,  while  barium  sulphate  remained  insoluble. 

The  soluble  matters  filtered  from  the  foregoing  precipitate  were 
freed  from  excess  of  caustic  barita  by  crystallisation.  From  the 
filtrate  all  barita  was  removed  by  excess  of  sulphuric  acid,  and 
from  the  solution  all  acetic  acid  was  expelled  by  distillation. 

From  the  cold  acid  liquid  alkaloids  were  removed  by  the  addi- 
tion of  phospho-wolframic  acid  as  long  as  a  precipitate  was 
produced.  This  precipitate  was  washed  with  water  containing 
5  per  cent,  of  sulphuric  acid,  and  then  decomposed  with  barita. 
The  solution  containing  the  mixture  of  alkaloids  was  further 
treated,  as  will  be  described  below. 

The  acid  filtrate  from  the  phospho-wolframates,  containing  the 
amido-acids,  w^as  freed  from  phospho-wolframic  and  sulphuric  acid 


by  barita,  and  evaporated  slowly  to  crystallisation.  It  deposited 
first  tyrosin,  then  a  mixture  of  leucin  and  tyrosin,  then  leucin 
and  small  quantities  of  other  amido-acids.  Then  a  syrupy  mass 
remained,  which  contained  yet  some  alkaloids,  besides  amido- 
acids.  Then  alkaloids  were  as  far  as  possible  removed  by  a  re- 
petition of  the  phospho-wolframic  acid  precipitation  just  described. 
Erom  the  liquid  more  leucin  was  obtained.  At  last  there  re- 
mained a  small  quantity  of  uncrijstallisahle  matter,  w^hich  was 
treated  as  follows : 

It  was  precipitated  b}^  mercuric  nitrate  and  sodium  carbonate. 
The  hdhj  ]jrecij)itate  was  washed  with  water  by  decantation,  etc., 
and  decomposed  by  hydrothion.  The  solution  on  evaporation 
left  a  colourless  gummy  mass  of  the  same  character  as  the  original 
matter.  It  will  be  further  treated  of  below.  The  mother-liquor 
of  the  mercury  precipitate  was  also  freed  from  mercury,  and 
found  to  contain  but  little  organic  matter. 

:  The  mixtures  of  tyrosin  and  leucin  were  united  and  warmed  with 
w^ater  containing  10  per  cent,  of  absolute  alcohol.  This  dissolved 
leucin,  and  left  tyrosin  undissolved.  The  limits  of  accuracy  of 
this  process  will  be  indicated  lower  down. 

,  Tyrosin  was  purified  by  solution  in  hydrochloric  acid,  treatment 
with  animal  charcoal,  and  precipitation  by  sodium  acetate  ;  the 
precipitated  tyrosin  was  crystallised  from  ammonia. 

Leucin  w^as  purified  by  combination  with  copper,  its  solution 
being  mixed  and  heated  with  copper  acetate  in  a  manner  the 
details  of  which  will  be  described  below.  In  the  course  of  this 
23rocess  a  new  leucin,  the  first  isomer  of  the  leucin  hitherto 
known, .  was  discovered,  and  from  its  sweet  taste  was  named 

The  copper-compounds  of  the  leucins  are  almost  insoluble  in 
cold  water,  more  soluble  in  boiling  water.  The  copper-compounds 
of  other  amido-acids  which  accompany  the  leucins  seem  all  to  be 
more  soluble  in  cold  w^ater,  particularly  those  of  lower  atomic 
weights  than  leucin. 

Glutaminic  and  asparaginic  acid,  which  have  been  obtained  by 
chemolysis  from  other  albuminous  substances,  have  not  yet  been 
isolated  from  the  products  of  chemol3'Sis  of  brain-albumen.  It 
remains  to  be  seen  whether  the  compound  alkaloids  w^hicli  have 
been  observed  Avill  on  long-continued  chemolj'sis  yield  these  acids. 
At  present  it  seems  as  if  the  l»arita  process  applied  to  brain. 



albumen  did  not  produce  them.  It  is,  however,  not  impossible 
that  they  may  be  formed  by  the  hydrochloric  acid  and  tin  process, 
which  evolves  them  easily  from  casein. 

Nitrogen  as  Ammonia  from  Neuroplastin. — Barita  chemolysis  of 
1 0  g.  and  distillation  gave  volatile  alkali,  which  was  neutralised 
by  hydrochloric  acid,  and  combined  with  platinic  chloride.  The 
dry  salt  was  redissolved,  and  left  0*0550  g.  insoluble  matter, 
while  the  soluble  double  salt  of  ammonio-platinic  chloride 
amounted  to  2-8760  g.  This  corresponds  to  0*1803  g.,  or  1*803 
per  cent.  N.  The  insoluble  platinum  salt  contained  0*0077  g.  N. 
This  quantity  of  nitrogen  is  far  below  that  obtained  by  the  same 
j)rocess  from  other  albuminous  matters.  It  approaches  that  ob- 
tained from  gelatin — namely,  2*55  per  cent.  It  is  less  than 
one-fourth  of  the  total  quantity  of  nitrogen  contained  in  the 
albuminous  substance. 

Total  of  Insoluble  Barium  Salts  obtained  from  10  [/.  Neurojjlastin. — 
These  salts  dried  at  110°,  weighed  4*1760  g.,  and  on  analysis  were 
found  to  have  the  following  constituents : 

Barium  sulphate  - 


Barium      _          .          .          .  - 


Phosphoric  acid  (PO^) 

•  0*099 

Oxalic  acid           _          _          .  . 


Sulphurous  acid     -          .          .  . 


Hydrothion           .          .           .  . 


Carbonic  acid  and  soluble  organic  matter  - 


Organic  insoluble  matter  - 




In  the  foregoing  experiment  about  1  per  cent,  of  phosphoric 
acid  was  obtained. 

Barium  retained  by  Amido- Alkaloid- Acid  Mixture. — The  mixture 
of  amido-acids,  alkaloids,  and  acids  from  which  all  excess  of 
caustic  barita  has  been  removed  by  carbonic  acid,  retains  a  con- 
siderable amount  of  barium  in  solution  ;  this  has  to  be  removed 
previous  to  the  distillation  of  the  volatile  acids.  The  amido  mix- 
ture from  10  g.  of  albumen  yielded  1*7830  g.  barium  sulphate, 
equal  to  1*0480  g.  Ba,  or  10*48  per  cent.  This  is  only  about  half 
the  quantity  of  barium  retained  in  the  chemolytic  products  of 
other  albuminous  substances,  ossein  excepted,  in  the  products  of 
which  the  barium  retained  amounts  to  13*2  per  cent. 


Quantation  of  Acetic  Acid  from  Neuroplastin. — The  acid  distil- 
late from  10  g.  of  brain-albumen,  chemolysed  as  above  described, 
yielded  0-1586  g.  barium  salt  (BaC^H^jO^,  At.  W.  ^  255)  equal  to 
0*074  acetic  acid,  or  0*74  per  cent.  This  is  only  one-fourth  of  the 
quantity  yielded  by  pure  albumen,  and  only  half  that  yielded  by 
ossein  or  ichthyocollin. 

Quantation  of  Tyrosin  from  Neuroplastin. — The  tyrosin  obtained 
by  the  chemolysis  of  10  g.  of  substance  was  separated  by  alcohol, 
recrystallised  from  ammonia,  and  dried  at  105°.  It  weighed 
0'122  g.  =  1-22  per  cent.  This  is  the  smallest  percentage  of 
tyrosin  as  yet  obtained  from  any  albuminous  substance  by  this 
process.  Tyrosin  is  retained  by  the  amido-mixture,  and  even  by 
crystallised  leucin.  The  quantities  of  tyrosin  actually  isolated 
must  therefore  be  considered  as  minima  until  absolutely  reliable 
methods  for  its  isolation  may  have  been  found  out. 

Leucins  from  100  g.  of  Ox-Nenroplastin. — They  were  combined 
with  copper  by  solution  in  boiling  water  and  addition  of  excess 
of  copper  acetate.  On  boiling,  a  precipitate  ensued,  which  was 
filtered  off  and  washed  with  cold  water  until  the  washings  were 
no  longer  blue.  This  precipitate  was  now  boiled  with  much 
water,  and  the  blue  solution  was  evaporated  to  dryness.  The 
residue  from  this  evaporation  is  product  No.  2,  while  the  salt 
which  remained  insoluble  in  boiling  water  {i.e.^  in  as  much  as  was 
applied)  constitutes  product  No.  1.  The  mother-liquor  of  the 
first  precipitate  was  evaporated  as  long  as  precipitates  Avere 
formed.    These  constitute  product  No.  3. 

Quantation  of  Copper  in  the  three  Froducts. 

No.  1  contained  -  -  -  19*05  per  cent.  Cu. 
No.  2  „  -  -  -  20-26  per  cent.  Cu. 
No.  3        „        -       -       -    19-5   per  cent.  Cu. 

The  latter  amount  of  copper  is  almost  that  required  by  cupric 
dileucin.  The  solution  obtained  by  decoction  of  the  first  preci^^i- 
tate  contained  probably  some  amido-acid  of  lower  atomic  weight, 
which  raised  the  amount  of  copper  to  20-26  per  cent. ;  while  the 
residual  salt  probably  contained  an  amido-acid  of  higher  atomic 
weight  than  leucin,  whereby  the  amount  of  copper  was  dei)ressed 
to  19*05  per  cent.  These  hypotheses  will  have  to  be  further 
tested  on  larger  quantities  of  material. 



Organic  Body  from  Mercuric  Chloride  and  Soda  Precipitate. 

The  white  precipitate  was  decomposed  with  hydrothion,  and 
the  solution  left  a  semicrystalHne  substance.  This  was  insoluble 
in  spirit  of  85  per  cent,  strength.  In  its  watery  solution  phospho- 
wolframic  acid  produced  no  precipitate,  showing  that  it  was  not 
and  did  not  contain  any  alkaloid.  Alkaline  copper  solution  on 
application  of  heat  gave  no  reaction.  Ferric  chloride  produced 
a  brown  precipitate,  soluble  in  excess  of  chloride,  with  an  intensely 
red  colour.  Ammoniacal  silver  solution  gave  no  precipitate,  but 
on  boiling  it  deposited  reduced  silver.  Copper  acetate  gave  no 
precipitate  even  on  addition  of  alcohol.  Acetate  of  lead  gave  a 
precipitate  only  after  the  addition  of  much  alcohol,  and  this 
compound  seemed  to  be  an  alcoholate.  When  dry  it  was  found 
to  contain  5 7' 8  per  cent,  of  lead.  It  was  therefore  probable  that 
the  body  was  not  and  did  not  contain  either  glutaminic  or  aspara- 
ginic acid. 

Properties  of  Common  Tasteless  Leucin  and  of  its  Copper-compound, 
studied  with  a  view  of  establishing  its  Diagnosis  from  its  Isomer 

Some  tasteless  leucin,  made  from  albuminous  matters  (not 
brain)  by  the  sulphuric  acid  process,  was  treated  with  cupric 
acetate,  and  the  first  precipitate  was  removed.  (In  this  any 
glycoleucin  would  have  been  contained.)  The  filtrate  from  the 
first  precipitate  on  evaporation  gave  a  precipitate  (termed  '  first 
precipitate  by  evaporation,'  being  second  precipitate  of  copper 
process),  which  was  decomposed  by  hydrothion.  The  solution,  on 
concentration,  gave  a  first  crop  of  crystals,  which  were  rhombic 
plates,  and  quite  tasteless. 

This  was  again  combined  with  copper,  and  the  precipitate  was 
filtered  off.  The  precipitate  was  now  boiled  with  water  re- 
peatedly until  it  was  completely  dissolved,  and  the  solution  was 
filtered  hot. 

Quantations  of  Sohdnliti/. 

(a.)  730  cc.  saturated  boihng  deposited,  mainly  immediately 
after  filtration,  and  only  to  a  small  extent  during  cooling  and 
standing  for  twenty-eight  hours,  blue  light  crystals,  which  when 
dry,  weighed  0'1790  g.,  indicating  a  deposit  of  1  part  out  of 
4,078  parts  of  boiling  water. 


(h.)  Of  the  clear  blue  filtrate  from  the  foregoing  operation 
630  cc.  were  evaporated  to  dryness,  and  left  0-1048  g.  of  blue 
compound,  showing  that  1  part  was  soluble  in  6,011  parts  of 
cold  water. 

(c.)  100  cc.  on  evaporation  left  0*0162  g.  residue,  equal  to  a 
solubility  of  1  part  in  6,172  parts  water. 

IiestiUs:  730  cc.  of  the  leucin  copper  solution  contained  while 
saturated  at  the  boiling  heat  0-3000  g.  of  salt;  of  this,  0'179  g. 
was  deposited  on  cooling,  while  0-1210  g.  remained  dissolved  at 
the  ordinary  temperature.  The  solubility  of  the '  salt  in  boiling 
water  is  therefore  1  part  in  2,433.  This  is  about  double  the 
solubility  of  glycoleucin  copper. 

It  is  generally  stated  in  chemical  writings  that  leucin  dissolves 
in  27  parts  of  water  at  the  ordinary  temperature.  I  find  by 
special  experiment  made  with  pure  tasteless  leucin,  that  1  part 
dissolves  in  30  parts  of  water  at  15°  C.  (Of  glycoleucin,  1  part 
is  soluble  in  82  parts  of  water  at  18°  C.)  It  requires  658  parts 
of  spirit  of  75  per  cent,  strength  for  solution.  Combination  with 
co2)per  therefore  reduces  its  solubility  very  greatly. 

The  immediate  deposition  of  crystals  from  a  saturated  leucin- 
copper  solution  filtered  hot  indicates  the  presence  in  the  com- 
pound of  ordinary  or  tasteless  leucin ;  the  hot  saturated  solution 
of  glycoleucin-copper  differs  from  the  former  in  this,  that  it  forms 
a  deposit  only  after  long  standing. 

StahiUti/  and  Begularity  of  Composition  of  Leucin  Copper  Compound. 

A  quantity  (2-3  g.)  of  crystallised  ordinary  tasteless  leucin,  of 
similar  origin  as  the  foregoing,  and  separated  from  copper  with 
which  it  had  been  combined,  was  a  second  time  converted  into 
the  copper  compound  by  means  of  copper  acetate.  The  compound 
was  extracted  several  times  with  boiling  water,  and  then  dis- 
solved entirely  in  a  sufficiency  of  boiling  water.  Soon  after 
filtration  there  separated  from  the  hot  solution  a  cnidcdUnc 
deposit,  which  increased  only  slightly  while  the  liquid  cooled  to 
the  ordinary  temperature  of  the  air.  The  precipitate  was  isolated 
and  dried  at  110°,  and  contained  19*15  per  cent.  Cu.  The  solu- 
bility of  this  precipitate  in  boiling  water  was  as  follows  :  200  cc. 
of  boiling  solution  saturated  by  long  boiling  with  excess  of  salt 
left' 0-0904  residue,  equal  to  a  solubility  of  1  part  in  2,212  parts 



of  boiling  water.  The  cold  solution  filtered  from  the  precipitate 
on  evaporation  left  a  residue,  which  showed  that  1  part  had 
been  dissolved  in  5,882  parts  of  water. 

The  soMo?i  in  which  the  crystalline  deposit,  described  in  the 
foregoing,  had  been  formed,  was  evaporated  to  a  small  bulk  as 
long  as  it  formed  any  deposit  while  hot,  and  then  allowed  to 
cool.  The  isolated  (here  termed  '  second ')  precipitate  dried  at 
110°,  contained  19-57  per  cent.  Cu.  200  g.  of  cold  water  dissolved 
0'0432  g.  of  this  compound,  which  is  equal  to  a  solubility  of  1  part 
in  4,630  parts  of  water. 

The  filtrate  from  the  second  dejjosit  just  described  was  evaporated 
to  dryness  to  obtain  the  remainder  of  the  leucin  compound.  Some 
copper  compound,  differing  in  appearance  from  the  leucin  com- 
pound, was  deposited  with  the  latter,  and  had  to  be  removed  by 
water  acidulated  with  a  little  acetic  acid.  This,  as  the  quantation 
of  the  copper  contained  in  the  compound  showed,  succeeded  onl}^ 
partially,  for  it  still  contained  20-39  per  cent.  Cu. 

Thus  it  will  be  seen  that  the  very  first  crystals  of  this  prepara- 
tion (reconstituted  a  second  time  as  copper-salt,  after  having  been 
constituted  the  first  time  as  copper  salt,  with  an  apparently  pure 
specimen  of  leucin)  contained  a  little  less  copper  than  is  de- 
manded by  theory ;  the  second  crystals,  obtained  by  concentra- 
tion, yielded  the  theoretical  amount  of  copper ;  and  the  third 
fraction  was  evidently  impure  by  the  admixture  of  a  copper  salt, 
which  was  perhaps  a  combination  of  an  amido-acid  of  lower  atomic 
weight  than  leucin. 

In  connection  with  this  it  deserves  to  be  mentioned  that  the 
presence  in  leucin  of  tyrosin  as  an  impurity  depresses  the  amount 
of  copper  which  will  be  found  in  the  copper  compound  made 
from  such  leucin.  11*2  g,  of  crystallised  leucin  were  treated  in 
boiling  watery  solution  with  copper  acetate,  and  the  deposit  was 
collected.  It  gave  on  analysis  (mean  of  two  quantations)  17-25 
per  cent.  Cu.  The  filtrate  on  further  evaporation  and  cooling 
gave  another  deposit,  which  on  analysis  was  shown  to  contain 
18-18  per  cent.  Cu.  Another  11-2  g.  of  the  same  leucin  as  that 
used  in  the  experiment  just  related,  was  dissolved  in  a  large 
quantity  of  warm  water,  and  allowed  to  cool  slowly,  when  it  de- 
posited a  sensible  portion  of  tyrosin.  The  leucin  was  now  removed 
by  the  copper  process,  and  the  compound  found  to  yield  the  theo- 
retical amount  of  copper.    The  mother-liquors  of  the  first  and  the 


second  part  contained  a  copper  salt  of  a  lower  amido-acid,  which 
had  a  sweet  taste,  but  was  not  glycoleucin. 

Note. — This  and  similar  copper  salts,  not  yet  exactly  identified, 
retain  tyrosin  in  solution.  When  the  copper  is  now  removed  by 
hydrothion,  the  filtrate,  reduced  to  the  same  bulk  as  the  original 
solution,  deposits  tijrosin.  This  first  deposited  tyrosin  gives  a 
good  mercurous  nitrite  test,  but  may  contain  some  of  the  following 
neiu  hody.  AVhen  the  mother-liquor  of  the  foregoing  tyrosin  is 
slightly  evaporated,  it  deposits  a  body  much  like  tyrosin,  crys- 
tallising in  microscopic  fine  needles,  but  giving  no  mercurous 
nitrite  reaction  ;  a  slight  rose-pink  which  appears  at  the  moment 
when  the  reagents  are  mixed,  disappears,  and  the  mixture  becomes 

Leucin  obtained  hy  Crystcdlisatmi  from  Amido-Mixture  from  Clie- 
mohjsis  of  Neurojjlastin. — Although  this  leucin  had  no  distinctly 
sweet  taste,  it  was  treated  with  copper  acetate  to  separate  any 
glycoleucin  which  might  be  contained  in  it.  It  was  dissolved  in 
hot  water  and  heated  to  boiling  ;  a  concentrated  solution  of  copper 
aceta.te  was  now  added  gradually  until  a  precipitate  was  formed. 
This  first  p'ecqntate  was  removed  by  the  filter.  To  the  filtrate 
was  added  copper  acetate  as  long  as  a  precipitate  was  produced, 
and  then  a  slight  excess  of  the  acetate.  The  mixture  was  allowed 
to  stand  and  deposit  the  second preciintate.  This  was  collected  on 
a  filter.  The  filtrate  was  evaporated  to  a  small  bulk,  and  deposited, 
particularly  on  cooling,  a  third  j^rodiid.  This  latter  appeared  the 
most  crystalline,  and  of  the  deepest  blue  colour. 

The  first  ^precipitate  was  then  boiled  seven  successive  times  with 
large  quantities  of  water  to  extract  the  common  leucin  copper 
compound,  and  leave  any  glycoleucin  copper  compound  insoluljle 
behind.  It  was  then  dried  on  the  filter  ;  lastly  in  the  air-bath  at 
110°,  and  analysed;  it  contained  19-60  per  cent.  Cu,  or  exactly 
the  theoretical  amount  of  cupric  dileucin. 

The  secoml  precipitate  was  boiled  with  nine  successive  large 
volumes  of  water,  and  what  remained  undissolved  was  analysed  ; 
it  contained  19-49  per  cent.  Cu. 

The  third  precipitate  which  crystallised  out  of  the  concentrated 
mother-liquor  of  the  first  and  second  precipitate,  was  finely  tritu- 
rated in  a  mortar,  washed  with  cold  water,  dried  at  110^,  and 
analysed  ;  it  contained  19-60  i)er  cent.  Cu  (again  exactly  the  tlieo- 
I'etical  amount  required  hy  cupiic  dileucin). 



The  first  and  second  precipitate  were  united,  suspended  in 
boiling  water,  and  decomposed  by  a  current  of  hydrothion.  The 
bulk  of  the  copper-sulphide  was  removed  by  filtration ;  the  hazy 
and  coloured  liquid  was  evaporated  to  collect  and  precipitate  some 
copper-sulphide  (which  is  frequently  imperfectly  precipitated  from 
neutral  organic  liquids),  and  after  final  filtration  evaporated  to 
crystallisation.  The  latter  process  was  aided  by  the  addition  of 
some  strong  alcohol.  The  crystals  were  collected,  and  recrys- 
tallised  from  water  and  alcohol  and  dried  in  the  air-bath.  On 
elementary  analysis  they  yielded  results  agreeing  closely  with  the 
theory  of  pure  leucin. 

Glycoleucin,  the  first  Chemohjtic  Isomer  of  Leucin,  its  Properties  and 

Glycoleucin  has  been  obtained  by  me  in  two  ways,  namely, 
synthetically,  and  by  the  chemolysis  with  barita  of  brain  albumens. 
I  have  not  obtained  it  from  animal  albuminous  matters  by  the 
sulphuric-acid  process,  which  yields  ordinary  tasteless  leucin. 

The  mode  in  which  it  is  separated  is  the  following  :  The 
mixture  of  the  several  leucins,  obtained  by  crystallisation  from 
the  amido-mixture,  is  combined  with  coj^per,  by  treatment  with 
acetate.  The  glycoleucin  copper  compound  is  mainly  deposited 
with  the  first  part  of  the  precipitate  ;  later,  a  mixture  is  deposited  ; 
lastly,  mainly  the  compound  of  ordinary  leucin.  The  copper 
compounds  which  result  are  then  exhausted  with  boiling  water. 
The  glycoleucin  copper  compound,  as  the  least  soluble,  remains 
behind,  and  is  ultimately  almost '  insoluble  in  boiling  water. 
Much  glycoleucin  copper  of  course  dissolves  with  the  compound 
of  ordinary  leucin.  The  latter  can  to  a  large  extent  be  isolated 
by  the  property  that  it  separates  from  the  boiling  saturated  solu- 
tion in  water  almost  immediately  after  filtration,  while  the 
saturated  boiling  glycoleucin  copper  solution  does  not  deposit  the 
excess  of  its  salt  until  after  long  standing.  It  will  be  evident 
that  these  processes  can  only  yield  small  quantities  of  material 
at  a  time.  Seven  specimens  of  glycoleucin  copper  Avere  decom- 
posed by  hydrothion,  etc.,  and  crystallised  separately.  Three  of 
the  crystallised  products  were  subjected  to  elementary  analysis, 
and  showed  the  identit}^  of  their  composition  with  that  of  leucin. 
The  seven  specimens  of  crystals  were  then  united  (they  weighed 
7-53  g.)  and  dissolved  in  boiling  water.    To  the  boiling  solution 


a  concentrated  cold  solution  of  cupric  acetate  was  added,  not  in 
excess.  A  sky-blue  precipitate  ensued,  and  was  filtered  off  while 
the  liquid  was  hot.  To  the  filtrate,  while  cooling,  a  further 
quantity  of  cupric  acetate  was  given,  until  no  further  precipitate 
was  produced. 

Freci/pitate  No.  1. — Dried  at  110°  contained  19-20  per  cent.  Cu. 
Frecijpitate  No.  2. — Dried  at  110°  contained  19 -45  per  cent.  Cu. 

An  eighth  specimen  of  pure  glycoleucin  was  combined  with 
copper,  and  the  comj^ound  on  analysis  gave  19 '45  per  cent,  of  Cu. 
The  mother-liquor  of  this  on  concentration  yielded  a  preparation 
which  on  analysis  was  found  to  contain  19-4:2  per  cent.  Cu. 

These  data  agree  pretty  closely  with  the  theory  of  monocupric 
dileucin,  which  contains  19'60  per  cent.  Cu  =  2(CgHjoN02)Cu,  or 

Solubility  of  the  Cupic  Salt  of  Glycoleucin  in  Cold  Water. — Pure 
salt  was  boiled  for  a  long  time  with  water ;  th^  mixture  was 
allowed  to  cool ;  when  quite  cold  the  solution  was  filtered  from 
the  compound.  200  cc.  at  16-5°  C.  on  evaporation  left  0*0228  g., 
equal  to  a  solubility  of  1  part  in  8,772  parts  of  water.  The 
solubility  of  ordinarj^  leucin  copper  is  1  part  in  6,172  parts  of 
water,  and  is  therefore  greater  than  that  of  glycoleucin  copper. 

During  the  operation  no  trace  of  reduction  or  blackening  was 
observed,  not  even  when  the  solution  of  the  compound  was  eva- 
porated to  an  extremely  small  bulk  with  excess  of  cupric  acetate. 
(This  constitutes  a  diagnostic  difference  from  the  bearing  of  a 
more  soluble  sweet  product  which  is  obtained  from  the  mother- 
liquors  of  the  amido-mixture,  and  during  the  evaporation  of  which 
with  coi)per  acetate  such  a  reduction  takes  place.) 

Solubility  of  the  Cujpric  Salt  of  Glycoleucin  in  Boiling  TFater. — 
200  cc.  of  the  boiling  solution  left  on  evaporation  to  dryness 
0-0449  g.,  or  1  part  dissolved  in  4,454  parts  of  boiling  water. 
This  is  about  double  the  solubility  of  the  salt  in  cold  water.  On 
cooling,  the  solution  becomes  only  slightly  opaque  ;  a  long  time 
is  required  for  it  to  deposit  the  salt  soluble  in  the  hot  as  a  visible 

The  glycoleucin  copper  compound  crystallises  in  minute  scales 
and  plates,  combined  in  masses  or  balls.  Many  of  the  scales  are 
clearly  rhombic,  others  rhoml^o-hexagonal. 

Elementary  Quantation  of  Glycoleucin,  p-eparecl  from  Insoluble 
Copi?er  Salt.  ■  -The  copper  was  removed  by  hydrothion,  and  the 


glycoleucin  obtained  pure  and  pearl-white  by  repeated  crystallisa- 
tion.   It  was  dried  over  calcium  chloride,  and  at  last  at  110"  C. 

At.  Wgts. 
6  C  72 
13  H  13 
N  14 
2  O  32 

131  0-00 

Glycoleucin  does  not  give  the  inosite  reaction  with  mercuric 

Solubility  in  Water  at  18°. — 100  parts  by  weight  of  solution 
retain  1*22  parts  of  glycoleucin  in  solution,  or  in  round  numbers 
1  part  is  soluble  in  82  parts  of  water.  Glycoleucin  is  therefore 
much  less  soluble  in  water  than  common  tasteless  leucin,  of  which 
1  part  requires  30  parts  of  water  for  solution  at  15°. 

The  sweet  taste  of  glycoleucin  is  less  easily  perceived  on  the 
crystals  than  on  their  saturated  solution.  Of  this  one  drop  will 
give  a  distinctly  sweet  taste  over  a  great  part  of  the  mouth.  The 
intensity  of  the  sweetness  is  not  much  less  than  that  of  inosite. 

A  New  Reaction  and  Compound  of  Cerebral  Tyrosin. 
I  have  shown  that  tyrosin  is  present  amongst  the  amidated 
bodies  extracted  from  the  brain,  though  in  small  quantities  only. 
It  is  also  a  product  of  the  chemolysis  of  neuroplastin,  and  cannot 
be  separated  so  completely  from  the  amido-mixture  as  is  desirable, 
and  as  is  generally  believed.  To  improve  the  processes  of  this 
separation  I  have  made  some  experiments  which  have  resulted  in 
the  following.  The  experiments  were  made  on  tyrosin  from 

Tyrosin  dissolved  in  hot  water  with  the  aid  of  caustic  soda  ley, 
on  addition  of  mercuric  chloride,  gives  a  deep  yellow  solution, 
and  no  precipitate.  On  cooling  the  mixture  becomes  turbid,  and 
on  reheating  a  yellow  precipitate  ensues.  The  solution  of  tyrosin 
must  be  dilute,  hot,  must  contain  excess  of  caustic  ley,  and  the 
i  mercuric  chloride  must  not  be  added  in  excess ;  if  excess  be 
added,  a  yellow  precipitate  is  immediately  produced.  If  to  the 
dilute,  hot,  alkaline  solution  of  tyrosin  mercuric  chloride  is  added 

Synojjsis  of  Theory  and  Data. 


Percent.  (a.)  {b.)  (c.) 

54-96  54-92  —  — 

9-92  10-02  —  — 

10-69  —  10-61  10-72 

24-43  _  _  _ 


gradually,  until  a  faint  yellow  precipitate  is  produced,  and  the 
solution  is  heated  and  allowed  to  stand,  the  slight  precipitate 
which  forms  on  heating  crj'stallises  entirely  in  golden-brown 
crystals,  and  is  Hg.20Cl2.  The  yellow  amorphous  precipitate, 
which  forms  out  of  the  j^ellow  solution  on  application  of  heat,  is 
entirely  soluble  in  excess  of  caustic  soda.  On  heating  the  solution 
to  boiling,  no  immediate  precipitate  is  now  produced.  If  the 
heating  and  addition  of  mercuric  chloride  are  done  very  gradually 
near  the  boiling-point,  until  the  yelloAv  fluid  becomes  opaque,  it 
sets  on  cooling  into  a  white  solid  jelly.  This  compound  is  dis- 
solved in  excess  of  caustic  soda,  the  solution  is  filtered,  and  the 
compound  is  then  reprecipitated  with  acetic  acid.  It  is  then 
jDerfectly  white.  The  compound  is  therefore  insoluble  in  weak 
soda,  soluble  in  great  excess  of  soda,  and  insoluble  in  dilute 
acetic  acid.  Dried  over  oil  of  vitriol  in  vacuo  and  analysed,  the 
compound  gave  the  following  data  : 

C  18-25 

1-  78 

2-  42 




Synopsis  of  Data  and  Theory. 



•by  At.  Wgts. 









2  +  HgO. 


or  2(Cc)HioN03  +  HgCl)  +  HgO,  or  expanded  in  the  following 
formula  : 




]  HgO. 


It  will  thus  be  seen  that  the  reaction  essentially  consists  in  a 
reduction  of  mercuric  to  mercurous  chloride,  which  remains  com- 
bined with  tyrosin ;  and  of  this  compound  two  molecles  are 
soldered  together  by  a  molecle  of  mercuric  oxide.  It  is  not 
intended  to  fix  the  exact  manner  in  which,  and  place  (in  the 
molecle)  at  which  this  union  is  effected.    The  reduction  of  the 



mercuric  to  mercurous  chloride  is  no  doubt  effected  by  that  part 
of  the  hydrogen  of  the  tyrosin  which  does  not  appear  in  the  })re- 
cipitate ;  in  other  words,  an  atom  of  hydrogen  is  substituted  by 
calomel.  For  this  latter  substitution  the  ordinary  didynamic 
character  of  mercury  affords  an  easy  opportunity,  but  for  the 
soldering  action  of  mercuric  oxide  the  metal  may  hypothetically 
be  allowed  to  possess  a  greater  number  of  dynamicities  than 

Mercuric  chloride  is  a  general  reagent  for  bodies  of  the  alkaloidal 
class.  In  this  capacity  it  produces  precipitates  in  almost  all  animal 
fluids  which  contain  albuminous  matters  or  their  derivates  down 
to  ammonia.  The  composition  of  these  precipitates  is  as  yet  little 
studied,  but  is  complicated  enough  to  have  deterred  inquirers 
from  ascertaining  it.  I  have  examined  some  such  precipitates, 
e.g.  from  the  extract  of  the  liver  in  kidney  diseases.  In  such,  the 
reduction  of  mercuric  to  mercurous  chloride  is  effected  massivel}^, 
but  only  a  part  of  the  calomel  produced  remains  in  combination. 
The  foregoing  is  a  key  to  the  study  of  such  combinations. 

New'  Alkaloids  oUained  from  Neuroplastm  hj  Chemohjsis. 

The  amido-mixture,  which  is  obtained  from  neuroplastin  by 
decomposition  with  barita  under  pressure,  yields  on  first  crystal- 
lisation leucin,  glycoleucin,  tyrosin,  and  some  amido-acids  of  lower 
atomic  weight  than  leucin.  But  there  remains  a  considerable 
part  of  the  mixture  which  does  not  crystallise  in  the  state  of 
mixture,  each  ingredient  of  which,  however,  seems  crystalline 
after  complete  separation.  I  have  isolated  two  of  the  ingredients, 
and  give  in  the  following  a  short  description  of  their  isolation 
and  their  properties. 

Mode  of  Isolation  of  Alkaloids  from  Armdo-Mixture. — The  mother- 
liquor  of  leucin  is  diluted,  acidified  with  sulphuric  acid,  and  mixed 
with  an  acidified  solution  of  phospho-wolframic  (syn.  phospho- 
tungstic)  acid,  as  long  as  a  precipitate  is  produced.  The  latter  is 
washed  with  water  containing  5  per  cent,  of  oil  of  vitriol,  by 
decantation,  ultimately  on  the  filler.  It  is  then  decomposed  with 
hot  barita  solution,  the  excess  of  barita  is  removed  by  carbonic 
acid,  and  the  resulting  solution  of  alkaloids  is  evaporated  to  a 
syrup.  This  product  has  the  following  properties  and  reactions  : 
It  is  strongly  alkaline ;  has  the  smell  of  sperma  ;  is  soluble  in 



ammonia  water ;  does  not  reduce  potassio-cupric  tartrate,  ^^lth 
hydrochloric  acid  and  gold  chloride  it  gives  a  copious  precipitate, 
which  is  insoluble  in  excess  of  acid,  easily  soluble  in  alcohol. 
Hydrochloric  acid  and  platinic  chloride  give  no  precipitate  in 
watery  solution,  but  in  alcohol  a  precipitate  is  produced.  Zinc 
chloride  gives  a  copious  white  precipitate,  which  is  soluble  in 
excess  of  the  chloride  and  in  hydrochloric  acid.  Silver  nitrate 
gives  a  voluminous  white  precipitate,  soluble  in  nitric  acid.  Tannin 
gives  a  voluminous  white  jorecipitate.  Mercuric  chloride  produces 
a  striking  phenomenon.  When  to  its  saturated  solution  a  drop  of 
alkaloidal  matter  is  added,  the  whole  surface  is  instantly  covered 
with  a  white  precipitate.  (The  matter  precipitated  is  therefore 
not  spermatin,  which  gives  only  a  turbidity  with  mercuric  chloride. 
Ann.  Chem.  Med.  i.  306.)  The  alkaloidal  matter  is  carbonated, 
as  on  addition  of  an  acid  carbonic  acid  is  evolved.  It  also 
contains  some  barium  not  precipitable  by  carbonic,  precipitable 
by  diluted  sulphuric  acid. 

Separation  of  the  Alkaloidal  Matter  into  two  Croups  ly  Absolute 
Alcohol. — When  the  syrupy  mixture  of  alkaloids  is  treated  with 
absolute  alcohol,  a  viscous  matter  remains  insoluble,  another 
j^ortion  dissolves  in  the  alcohol.  The  matter  insoluble  in  alcohol 
retains  its  solubility  in  water.  The  matter  soluble  in  alcohol 
gives  with  platinic  chloride  a  copious  precipitate  of  a  double  salt. 
This  is  not  changed  by  alcohol,  but  is  altered  quickly  by  water. 
It  fuses  after  evaporation  of  the  alcohol.  Placed  in  water  it 
practically  dissolves,  a  part  remains  undissolved.  The  solution 
in  water  continues  to  form  deposits,  for  weeks,  of  the  insoluble 
salt.  Owing  to  this  lability  I  have  not  examined  these  two 
platinum  salts  any  further. 

From  the  viscous  matter  precipitated  by  alcohol  there  was. 
obtained  by  a  process  of  continued  crystallisation  a  white  crys- 
tallised alkaloid,  very  soluble  in  water,  easily  soluble  in  hydro- 
chloric acid.  The  hydrochlorate  evaporated  to  dryness,  and 
redissolved  in  water,  crystallises  from  concentrated  solution. 
From  spirit  this  hydrochlorate  crystallises  still  better.  The  spirit 
solution  may  be  mixed  with  ether  without  yielding  a  precipitate. 
But  the  crystals  of  the  hydrochlorate  are  not  very  soluble  in 
ether  and  may  be  washed  with  it.  The  salt,  mixed  with  mercuric 
chloride  and  then  with  caustic  soda,  gives  a  white  precipitate 
soluble  in  excess  of  the  soda. 



Eleriientanj  Quantation  of  this  neiv  Alkaloid. — After  removal  of 
the  hydrochloric  acid  the  free  body  crystallises  in  balls  of  needles. 
Dry  at  110°. 

The  analyses  lead  to  the  following  provisional  theory  : 

Found  Percents.  -^At.  Wts.  -^N  =  l. 

C       52-99  4-4158  6-3 

H        9-03  9-03  12-9 

N        9-896  0-7068  1- 

0       28-084  1-755  2-5 


These  relations  of  elements  remind  of  a  leucein  (rather  than  a 
leucin),  with  which  probably  a  small  quantity  of  a  higher  homo- 
logue  is  mixed. 

Separation  of  the  Alkaloidal  Matter  into  tico  Groups  hy  Cupric 
Acetate  and  Absolute  Alcohol. 

When  the  mixture  of  alkaloids  is  dissolved  in  little  water  and 
mixed  with  a  saturated  solution  of  cupric  acetate  and  warmed,  no 
precipitate  of  leucin  copper  ensues  if  the  process  of  precipitation 
by  the  phosphotungstic  acid  has  been  correctly  conducted.  On 
continued  warming  some  brown  cuprous  and  dark  cupric  oxide 
are  deposited.  The  deep  blue  solution  filtered  from  all  deposits 
is  mixed  with  absolute  alcohol  as  long  as  this  agent  produces  a 
precipitate.  This  is  the  copper  compound  of  a  new  alkaloid, 
which,  without  further  purification,  on  analysis  gave  the  following 
preliminary  results  : 

Synojms  of  Result  and  Theory. 

Percents.  -i-At  Wgts.  -^Cu  =  l. 

C     38-23  3-186  12-95 

H      5-91  5-91  24- 

Cu  15-60  0-246  1* 

N    10-61  0-757  3- 

0    29-65  1-853  7-53 


Leading  to  formula  C^.^H^sCuNgO^,  or  Ci2H23N30g  +  CuO.  The 
salt  has  a  very  light  blue  colour ;  it  is  easily  soluble  in  water,  and 
the  solution  has  a  very  dark  blue  colour. 



The  alkaloids  which  are  soluble  in  absolute  alcohol  in  the 
presence  of  cupric  acetate  have  not  yet  been  isolated.  They  con- 
tain, of  course,  the  bodies  which  give  the  platinum  compounds 
above  described.  I  have  subjected  them  to  numerous  reactions, 
and  have  isolated  some  peculiar  bodies.  But  they  must  be  pro- 
duced in  quantity  before  they  can  be  studied  with  advantage. 

These  alkaloids  were  not  observed  by  Schiitzenberger  in  the 
researches  on  the  chemolysis  of  various  albuminous  substances 
of  which  I  have  given  an  abstract  in  Ann.  Chem.  Med.  i., 
pp.  20-44.  They  will,  therefore,  have  to  be  added  to  the  list  of 
terminal  cleavage  products. 





The  ash  of  the  fresh  grey  tissue  of  man  amounts  to  about  1  per 
cent.  ;  that  of  white  tissue  is  about  1  '7  per  cent.  ;  the  same  relations 
are  observed  in  the  grey  and  white  tissues  of  the  ox.  From  the 
former  data  it  is  apparent  that  an  ordinary  human  brain  contains 
from  18  to  20  g.  of  ash  or  incombustible  residue.  This  residue  con- 
sists, however,  to  the  extent  of  about  48  per  cent,  of  phosphoric 
acid,  of  which  about  one-fifth  is  in  the  free  state,  while  four-fifths 
are  in  combination.  The  greater  part  of  this  phosphoric  acid  is 
unquestionably  derived  from  the  phosphatides,  and  has  replaced 
nearly  all  the  more  volatile  acids,  such  as  carbonic,  hydrochloric, 
and  sulphuric  acid.  But  even  so  the  phosphoric  acid  included  in 
the  1  "7  per  cent,  of  incombustible  matter  is  certainly  less  than  one- 
third  of  the  phosphoric  acid  which  is  present  in  the  phosphatides. 
It  is  therefore  clear  that  a  great  portion  of  the  phosphorus  present 
in  brain  is  volatilised  in  the  course  of  the  ordinary  method  of  com- 
bustion. This  method,  therefore,  actually  leaves  only  the  bases 
in  an  approximately  complete  manner.  100  parts  of  acid  brain- 
ash  contain  32  parts  of  potash,  11  parts  of  soda,  and  some  lime 
and  magnesia,  for  which  we  do  not  give  figures,  because  we  have 
none  of  our  own,  but  know  that  those  given  by  others  are  in 
correct.  The  analysis  of  the  mineral  ingredients  of  the  brain 
will  therefore  have  to  be  resumed  in  the  manner  indicated  in 
the  chapters  which  treat  of  the  purification  of  the  phosphatides, 
the  cerebrosides,  and  the  final  water-extracts.  These  latter,  we 
know  already,  contain  sodium  chloride,  and  sulphates,  and  phos- 
phates, besides  salts  of  organic  acids.    The  cerebrosides  and  the 


phosphatides  remaining  mixed  with  them  have  a  great  tendency 
to  retain  potash,  in  a  form  which  is  not  precisely  known.  The 
phosphatides  retain  salts  and  oxides,  amongst  them  lime,  as 
shown  in  a  previous  chapter.  Future  analyses  for  the  mineral 
salts  will  therefore  have  to  be  applied  to  four  different  materials, 
the  neuroplastin,  the  phosphatides,  cerebrosides  and  cerebrinacides, 
and  the  ultimate  water-extracts. 






Grey  tissue  was  careful!}^  cut  from  the  surface  of  both  hemi- 
spheres, and  from  the  anterior  and  posterior  lobes  of  each. 
6 '2 395  g.  were  dried  at  95°  until  the  weight  was  constant.  The 
substance  was  repeatedly  cut  up  with  a  knife.  The  dry  residue 
weighed  0*9193  g.  =  14-73  per  cent.  The  water  lost  amounted  to 
5-3202  g.  =  85-27  per  cent. 

For  the  following  operations  another  quantity  of  grey  tissue, 
amounting  to  46  g.  fresh,  was  cut  from  all  parts  of  the  brain.  It 
was  extracted  five  times  with  boiling  spirit  in  a  flask  attached  to 
a  reflux  cooler. 

The  albuminous  residue^  dry,  weighed  3-5  g.,  equal  to  7-6  per 
cent,  of  the  fresh  grey  tissue.  It  wus  analysed  for  sulphur  and 
phosphorus.  1*5304  g.  were  burnt  with  addition  of  barita-water, 
and  gave  0-0024  BaSO^=  0-02  per  cent,  sulphur,  and  0*0325 
magnesium  pyrophosphate  =  0-60  per  cent,  phosphorus. 

The  deposit  which  the  spirit  made  on  cooling  (cerebrins,  etc.) 
weighed  0*3  g. 

The  spirit  solution,  evaporated  to  half  its  bulk,  gave  a  (second) 
deposit  which  weighed  0*1  g. 

The  filtrate  from  this  was  evaporated  to  a  small  volume,  and 
deposited  a  (third)  deposit  weighing  0*7  g. 

The  foregoing  deposits  (0*3  +  0-1+0*7,  total  =1*1  g.)  were 
extracted  with  ether.  There  remained  0*2  insoluble,  0-9  were 
soluble  in  ether.  The  matter  soluble  in  ether  (previously  de- 
posited from  spirit)  amounted  to  1*950  per  cent,  of  the  fresh 


tissue,  while  the  matter  insohible  in  ether  (cerebrius  mainly) 
amounts  to  onl}'  0434  per  cent,  of  the  tissue. 

The  last  oily  matter^  which  could  not  be  filtered  from  the  water- 
extract  in  which  it  was  suspended,  was  precipitated  with  lead 
acetate ;  the  curded  precipitate  was  collected  on  a  filter. 

The  irrecipitate  of  lead  salts  contained  the  phosphorised  organic 
compounds  and  sulphuric  and  phosphoric  acid  from  the  inorganic 
salts.  It  was  washed  while  being  continuously  stirred  with  water 
to  which  a  little  lead  acetate  had  been  added.  It  was  next  ex- 
tracted with  absolute  alcohol.  The  alcoholic  solution  contained 
all  the  lecifhiii  (with  some  lead).  The  dry  matter  weighed 
0-73  g. 

The  insoluble  in  alcohol  residue  was  completely  dried  and  ex- 
tracted with  ether.  The  solution  on  distillation  left  all  Jcejjhalin 
lead,  which  weighed  0"22  g. 

The  insoluble  in  ether  residue  was  extracted  with  boiling 
alcohol,  which  dissolved  matters  which  when  diVj  weighed  0"03  g. 

The  residue  from  the  three  extractions  with  alcohol,  ether,  and 
boiling  alcohol  was  mainly  an  inorganic  lead  salt.  It  was  ex- 
hausted with  dilute  nitric  acid,  and  the  insoluble  residue  was 
recognised  as  lead  sulphate.  The  matter  soluble  in  nitric  acid 
was  anal3^sed  for  phosphorus  by  ammonium  molybdate,  etc.,  and 
gave  0-0049  P.  T\\q  ijliosphoric  acid  thus  indicated  was  evidently 
combined  with  alkalies  in  the  grey  tissue. 

The  lead  salts  from  the  mixture  of  the  last  oily  matter  and 
watery  extract  obtained  as  just  described  are  liable  to  contain 
some  inosite  lead  as  an  insoluble  compound.  When  this  is  decom- 
posed in  warm  absolute  alcohol  by  hydrothion,  an  alcoholic 
solution  is  obtained  from  which,  on  long  standing,  and  again 
after  concentration,  inosite  is  deposited  in  crystals.  I  have  care- 
fully identified  these  crystals,  by  their  taste,  their  shape,  and 
their  reaction  with  mercuric  nitrate.  It  is  therefore  clear  that 
inosite  can  be  precipitated,  under  the  conditions  prevailing  in 
this  research,  by  neutral  acetate  at  least  in  part.  Its  complete 
precipitation  can  be  effected  only  by  hasir  acetate,  and  that  with 
the  aid  of  ammonia. 

The  v:aterij  solution  was  freed  from  lead  by  hydrothion,  con- 
densed to  expel  acetic  acid,  acidified  with  sidphuric  acid,  and 
extracted  Avith  ether.  The  extract  gave  by  the  usual  treatment 
zinc  lactate  in  crystals,  which  weighed  0-07  g.,  equal  to  0-04.52  g. 



lactic  acid  in  44  g.  grey  tissue,  or  0-102  per  cent. ;  in  round 
numbers,  one  part  of  lactic  acid  in  a  thousand  of  grey  tissue. 

The  solution  from  which  lactic  acid  had  been  extracted  was 
treated  with  ammonium  carbonate  in  excess,  and  gave  clear 
indication  of  the  presence  of  calcium.  The  filtered  solution  was 
boiled  to  expel  ammonia,  and  then  treated  with  phosphomolybdic 
acid.  A  precipitate  of  alkaloids  or  extractives  was  obtained 
weighing  0"530  g. 

From  the  filtrate  all  phosphomolybdic  and  sulphuric  acid  were 
removed  by  barita.  The  filtrate  treated  in  the  usual  way  and 
evaporated  to  dryness  left  a  residue,  being  inosife  and  carbonates 
of  alkalies  weighing  0*69  g.  It  gave  with  mercuric  nitrate  the 
inosite  reaction.  The  residue  was  dissolved  in  water,  and  pre- 
cipitated by  lead  acetate  and  ammonia.  The  precipitated  inosite 
lead  was  isolated  and  decomposed  by  hydrothion. 

The  mother-liquor  of  inosite  lead  was  freed  from  lead,  eva- 
porated, burnt,  etc.,  and  left  mixed  carbonates  of  alkalies, 
which  were  transformed  into  chlorides  =  0-2560.  Out  of  this 
quantity  platinic  chloride  precipitated  0-070  double  chloride 
=  0-0112  K  =  0-0250  per  cent.  K  in  grey  tissue.  The  remaining 
sodium  amounted  to  0*0920  per  cent,  of  grey  tissue, 
Synoims  of  the  Besults  of  Analysis  of  Grey  Tissue  of  Human  Brain. 


Water  expelled  at  95° 

-  85-270 


-  7-608 

Ether   extracts,   kephalin,  and 


(and  cholesterin  "?) 

-  1-950 

Cerebrins  and  myelin 

-  0-434 

Lecithin  \ 

Kephalin  /■  from  last  oily  - 
Myelin     j  (and  cholesterin  ?) 

-  0-780 

Inosite     -          _  - 

-  0-193 

Lactic  acid 

-  0-102 


Sulphuric  acid 


Phosphoric  acid,  H3PO4  - 

-  0-017 


-  0-025 

Sodium    -          -  - 

-  0-092 


-  0-500 

Loss  in  operations 

The  loss  in  operations  is  very  large,  amounting  to  almost  a 
quarter  of  the  entire  solids.  It  is  mainly  incurred  through  the 
difficulty  which  there  is  of  separating  the  last  oily  matter  from 


the  matter  soluble  in  water.  But  other  operations  equally  involve 
as  yet  unavoidable  loss.  The  construction  of  suitable  apparatus 
for  ether  extraction  would  only  partly  avoid  the  loss  by  ether 
extraction,  as  in  this  process  the  main  difficulty  is  filtration. 


The  parts  to  be  analysed,  amounting  to  66  g.,  were  cut  from 
the  centre  of  the  hemispheres  and  corpus  callosum.  They  were 
triturated  to  a  pulp,  mixed  with  spirit,  and  extracted  six  times 
with  boiling  spirit. 

The  sinrit  extract  deposited  a  white  cerehriii  substance  on  cooling, 
which  was  collected  and  washed.  It  was  then  extracted  with 
large  volumes  of  ether  and  filtered  again.  It  weighed,  dried  at 
70",  4*5615  g.,  equal  to  6-91  per  cent,  of  the  fresh  white  brain- 
substance.    Further  treatment  of  the  cerebrin  bodies  see  below. 

Ether  extract  of  the  cerebrin  deposit. — The  ether  was  distilled  off, 
the  concentrated  solution  was  filtered  from  a  trifling  deposit,  and 
distilled  to  dryness.    The  residue  weighed  2-4150  g. 

The  ether  extract  of  the  albuminous  substance  (made  after  exhaustion 
by  spirit  and  drying)  on  concentration  deposited  a  few  oily  drops, 
and  on  distillation  to  dryness  left  a  residue  weighing  0*0350  g. 
It  became  dark,  and  existed  only  as  a  minute  brown  coating  on 
the  glass,  possibly  a  mere  trace  of  phosphorised  substance,  too 
small  in  quantit}''  for  further  treatment. 

The  neurojplastin  residue  was  dried  and  weighed,  after  the  treat- 
ment with  ether,  5-70  g.,  equal  to  8*63  per  cent,  of  original 
white  brain-substance. 

The  spirit  extract  which  had  deposited  the  white  matter  was 
concentrated  twice  in  succession,  and  after  each  concentration 
deposited  a  semi-crystalline  buttery  matter.  Of  this  the  ether 
extract  weighed  5-1730  g.,  while  the  part  insoluble  in  ether 
weighed  0*1400  g.  Of  this  a  part  was  soluble  in  boiling  spirit, 
and  deposited  on  cooling,  while  a  dark  part  was  insoluble  in  boil- 
ing spirit,  and  contained  some  inorganic  matter  and  phosphorus. 

The  cerebrin  mixture  above  described,  weighing  4*5615  g.,  was 
dissolved  in  boiling  absolute  alcohol,  when  0*1815  g.  of  coloured 
matter,  which  was  insoluble  in  benzol,  and  therefore  was  not 
stearoconote,  remained  undissolved,  =0*275  per  cent,  of  tissue. 
(It  amounted  to  3*9  per  cent,  of  the  cerebrin  mixture,  and  besides 
some  slight  impurity  was  neuroplastin. ) 



The  dissolved  part  deposited,  on  cooling  and  standing,  phrenosin, 
kerasin,  cerebrinic  acid,  with  some  phosphorised  matter,  and 
retained  a  phosphorised  matter  in  solution.  The  dry  cerebrins 
weighed  together  2-6030  (equal  to  3*94,  in  round  numbers 
4  per  cent.,  of  the  white  tissue). 

The  alcoholic  solution  from  which  these  cerebrins  had  been 
deposited,  measuring  750  cc,  contained  1-770  g.  of  matter  dis- 
solved, being  phosphatides,  amidolipotides,  cerebrosides  and 
cerebrinacides.  With  this  some  attempts  at  identification  and 
quantation  were  made.  Out  of  one  half,  375  cc,  a  precijjitate 
was  obtained  with  the  aid  of  alcoholic  platinic  chloride  ;  the  pre- 
cipitate, dried  at  65°,  weighed  0-4524  g.,  and  contained  phosphorus 
=  2-52  per  cent.  The  second  375  cc.  were  precipitated  with 
alcoholic  cadmic  chloride;  the  precipitate  weighed  =0-2965,  and 
contained  phosphorus  =  4*78  per  cent. 

The  cadmium  salt  therefore  contained  much  more  phosphorus 
than  the  platinum  salt ;  in  other  words,  they  contained  different 
organic  ingredients.  Moreover,  the  precipitants  brought  down  only 
about  one-sixth  part  of  the  matter  in  solution  in  absolute  alcohol. 
The  mother-liquors  were  concentrated  and  made  deposits,  which 
were  examined,  but  the  results  were  not  of  a  nature  to  be  quoted. 

The  substances  which  remain  dissolved  in  much  absolute 
alcohol  amount  to  2-6  per  cent,  of  the  white  tissue. 

The  last  oily  matter  which  was  suspended  in  the  aqueous  extract 
could  not  be  separated  by  filtration.  This  is  one  of  the  greatest 
difficulties  of  brain  analj^sis,  and  will  have  to  be  overcome  by 
further  discovery.  In  the  interval  I-  have  adopted  the  following 
process,  which  is  efficient  in  all  directions  except  on  the  point  of 
inosite,  as  I  have  already  stated  above.  The  mixture  was  treated 
with  lead  acetate ;  the  precipitate  was  dried  (and  weighed  0-7  340  g.). 
It  was  extracted  with  cold  absolute  alcohol.  (The  extract  weighed 
0-4802  g.)    It  was  mainly  lecithin,  with  some  lead. 

The  part  insoluble  in  cold  absolute  alcohol  was  extracted  with 
ether ;  the  solution  left  a  residue  of  kephalin  lead,  weighing 
0-2030  g. 

The  part  insoluble  in  ether  was  mainly  myelin  lead,  but  con- 
tained some  sulphuric  and  phosphoric  acid.  It  weighed  =0-1970  g. 

The  watery  filtrate  from  the  lead  precipitate  was  freed  from  lead 
by  hydrothion  evaporated  to  dryness,  and  left  a  residue  0*9260  g. 
This  was  redissolved  in  little  water,  and  acidified  with  sulphuric 


acid.  The  mixture  was  extracted  with  ether,  and  the  extract 
treated  for  lactic  acid,  with  zinc,  etc.  The  zinc  lactate  crystallised 
white,  weighed  =0*0707  g.,  dried  over  oil  of  vitriol  in  vacuo. 

The  acid  solution  from  which  the  lactic  acid  had  been  extracted 
was  precipitated  with  phosphomolybdic  acid,  and  the  precipitate 
filtered  off  and  dried  =0-1270  g. 

The  filtrate  from  this  was  treated  with  barita,  etc.,  and  after 
treatment  with  ammonium  carbonate  and  evaporation  left  a 
residue  weighing  0*7500.  This  was  redissolved  in  water  and 
precipitated  with  basic  lead  acetate.  Inosite  lead  w^as  isolated 
and  decomposed  with  hydrothion.  The  dry  inosite,  crystallised, 
weighed  =0-1420. 

The  mother-liquor  was  freed  from  lead,  evaporated  to  dryness, 
burnt,  and  the  residue  weighed  =0-171  g.  ;  of  the  metals  in  this, 
17*67  per  cent,  were  potassium,  and  82*33  per  cent,  sodium. 

Synopsis  of  the  EesuUs  of  Analysis  of  White  Tissue  of  Human  Brain. 

Water  expelled  at  95°        -          -          -  -  70-230 

Neuroplastin          -          -          -          -  -  8*630 

Ether  extracts,  kephalin,  lecithin,  and  cholesterin  -  11*497 

Cerebrins  and  myelin         -          -          -  -  6*910 

Insoluble  in  ether  from  buttery      -          -  -  0-212 

Lecithin  (lead)        -----  — 

Kephalin  (lead)       -----  — 

Myelin  (lead)         -  -  -  -  -  — 

Water-extract,  1*403  per  cent,  consists  of    -  -  — 

Lactic  acid  ------  0*0456 

Inosite        -  -  -  -  -  -  02151 

Alkalies  (carbonates)  -  -  -  -  0*1717 

The  separation  of  the  ether  extracts  into  their  constituents  was 
also  carried  out,  and  the  results  will  be  stated  lower  down. 


Absolute  Weight 
Division  of  the  Brain.        Weight  in  in 

Air.  Water. 

1.  Eight  hemisphere  -  589-035  20*820 

2.  Left  iiemisphere    -  595-823  21-600 

3.  Cerebellum   -       -  135-172  5-030 

4.  Mesenkephalon     -  33*950  1*250 

5.  Sclerotic  part        -  3*630  0*150 

Entire  Brain  -  1357-610    48-850    1308-700  1-037 

Loss  of  cj  'c 

Weight  in  Specie 

Water,  ^""^^'^y- 

568'215  1*037 

574*223  1*038 

130-142  1-039 

32-700  1*038 

3-480  1*043 



Quantation  of  the  Specific  Gravihj  of  White  Tissue  and  Grey  Tissue 
of  the  Humctn  Brain. 

These  specific  gravities  were  ascertained  by  suspension  of  the 
parts  in  water,  etc.  (grammes  at  16°). 

Wgt.  in  Air. 

Wgt.  in  Water. 

Spec.  Grav. 


















1  -036 







Greij  Tissue. 

Wgt.  in  Air. 

Wgt.  in  Water. 

Spec.  Grav. 










The  foregoing  data  have  been  arranged  in  the  order  of  decreas- 
ing sjDecific  gravities.  This  led  at  once  to  an  inverse  order  in  the 
column  denoting  weights  in  air.  Only  two  figures  out  of  eleven 
do  not  absolutely  take  the  places  which  they  would  occupy  if  the 
order  of  increase  in  the  first  column  was  inverse  as  that  in  the 

It  therefore  appears,  what  has  also  been  confirmed  by  many 
other  experiments,  some  to  be  related  below,  that  the  sjMcific 
gravity  of  white  and  grey  tissue  of  the  brain  is  found  the  higher,  the 
smaller  is  the  quantity  of  hrain-tissue  employed  in  the  experiment.  Now, 
as  the  pieces  of  tissue  which  can  be  employed  in  the  experiments 
are  limited  in  size  by  the  arrangement  of  the  relative  tissues 
in  the  brain,  it  is  clear  that  the  specific  gravity  quantations 
of  brain-substance  in  water  can  only  be  approximately  correct. 
The  variations,  no  doubt,  depend  upon  a  reaction  between  the 
surface  of  the  piece  of  tissue  immersed  and  the  water  which  sur- 
rounds it.  The  water  takes  up  some  soluble  albumen  and  some 
salts,  and  the  piece  of  brain-tissue  immersed  assumes  a  glazed 
appearance.    It  is  evident  from  this  that  the  greater  the  surface 


of  the  piece  under  observation  to  its  volume^  the  greater  will  be 
the  effect  of  this  source  of  error.  The  error  will  further  be 
influenced  by  the  length  of  time  during  which  the  piece  of  tissue 
is  immersed,  and  consequently  variations  will  arise,  even  when 
pieces  of  equal  size  are  examined,  from  the  interference  of  the 
accident  of  quicker  or  slower  weighing.  It  is  further  doubtful 
whether  white  and  grey  tissues  will  be  equally  influenced  by 
water  in  the  same  time,  even  when  their  bulks  are  equal.  It  is 
further  not  j^roved  that  either  the  grey  or  the  white  tissue  is  so 
homogeneous  in  any  part  of  the  brain  as  is  assumed  for  the 
purposes  of  comparison.  It  is  therefore  clear  that  specific  gravity 
estimates  of  brain-tissue  in  water  have  only  an  approximative 
and  no  absolute  mathematical  value.  Such  estimates  must  there- 
fore be  made  with  the  aid  of  fluids  of  well-known  specific  gravity, 
which,  while  they  make  contact  with  the  brain-tissue,  do  not 
provoke  in  it  any  chemical  or  physical  changes. 

Quantations  of  the  Sjmfic  Gravities  of  White  and  Grey  Tissue  from 
different  parts  of  the  Brain. 

White  Tissue  of  Hemispheres. 

(a.)  Quantations  by  the  Piknometer  : 

Absol.  Wgt.  Subst.  +  Pik.  Pik.  +  Water. 

0-4526  61-9300  61-9120 

0-2817  61-9342  61-9198 

{b. )  Quantations  hy  Suspension  in  Water  : 

Absol.  Wgt.  Wgt.  in  Water.  Spec.  Grav. 

0-  6859  0-0310  1-044 

1-  0479  0-0394  1-039 
3-7845  0-1319  1-036 
9-5362  0-2740  1-030 

Spec.  Grav. 

Grey  Tissue  of  Hemisphere, 
(a.)  Quantation  by  the  Piknometer: 

Absol.  Wgt.  Subst.  +  Pik.  Pik.  +  Water.  Spec.  Grav. 

0-3117  61-9146  •  61-9039  1-039 

(b.)  Quantations  by  Suspension  in  Water : 

Absol.  Wgt.  Wgt.  in  Water.  Spec.  Grav. 

0-6628  0-0243  1-038 

14-4592  0-3810  1-027 



TFhite  Tissue  of  Cerebellum, 
(a. )  Quantation  hj  Pihnometer  : 

Absol.  Wgt.  Subst.  +  Pik.  Pik.  +  Water.        Spec.  Grav. 

0-5900  61-9240  61-9039  1-037 

{!).)  Quantation  by  Suspension  in  Water  : 

Absol.  Wgt.  Wgt.  in  Water.  Spec.  Grav. 

0-8650  0-0400  1-048 

White  Tissue  of  Mesenkeplialon. 
(a.)  Quantation  by  Piknometer  : 

Absol.  Wgt.  Subst.  +  Pik.  Pik.  +  Water.        Spec.  Grav, 

0-6849  61-9252  61*9039  1-032 

(b.)  Quantation  by  Suspension  in  Water  : 

Absol.  Wgt.  Wgt.  in  Water.  Spec.  Grav. 

0-5128  0-0258  1-053 

Synopsis  and  Averages  of  the  Specific  Gravities  observed  in  the  three 
Series  of  Observations  detailed  in  the  foregoing,  without  reference 
to  repetition  of  the  same  numbers  or  to  quantities  on  which  they 
were  observed. 

I.  White  Tissue. 

1.  1-054  5.  1-044  9.  1-036 

2.  1-053  6.  1-051  10.  1-032 

3.  1-048  7.  1-039  11.  1-030 

4.  1-046  8.  1-037 

Mean  specific  gravity  of  white  tissue  =  1-041. 

II.  Grey  Tissue. 

1.  1-039  2.  1-038  3.  1-027  4.  1-025 

Mean  specific  gravity  of  grey  tissue  =  1-032. 
Specific  gravity  of  entire  brain  (four  parts)  =  1*037. 

The  foregoing  figures  do  not  difi'er  much  from  those  accepted 
by  other  observers.  The  specific  gravity  of  white  tissue  is  the 
same  as  that  commonly  allowed  in  physiological  treatises,  namely 
1-041,  while  the  specific  gravity  of  grey  tissue  is  1-032  instead  of 
that  commonly  allowed,  namely  1-034.  But  when  it  is  con- 
sidered that  what  must  theoretically  be  assumed  to  be  the  best 
observations  of  the  specific  gravity  of  white  tissue,  namely  those 
on  the  largest  volume,  do  only  give  1  -030  as  the  value,  while  grey 


tissue  under  the  same  limitation  gives  1*027,  it  is  impossible  to 
avoid  the  suspicion  that  all  specific  gravity  estimates  hitherto 
made,  including  the  foregoing,  are  vitiated  by  a  fundamental 
fault  of  method,  or  by  several  faults,  as  above  indicated.  These 
probable  faults  have  for  the  first  time  been  observed  in  the 
course  of  the  present  researches,  and  there  has  been  no  time  for 
remedying  the  inconveniences  arising  out  of  the  observation. 

In  1876,  I  communicated  a  then  new  method  for  estimating 
the  proportion  between  white  and  grey  tissue  in  the  brain 
(an  important  physiological  problem,  which  seems  anatomically 
quite  insoluble)  by  a  calculation  from  the  four  factors, 
absolute  weight  of  the  brain,  specific  gravity  of  the  entire  brain, 
and  specific  gravities  of  each  white  and  grey  tissue.  This 
method  still  has  its  future,  if  the  diff'erence  between  the  specific 
gravity  of  white  and  grey  tissue  be  not  ultimately  found  too 

In  its  execution  the  following  formula  may  be  used  : 

Vwip  —  q)  .      ,  .  , 
X  =    — — -lii,  m  which 

X  =  quantity  of  white  m^atter. 
P  =  absolute  weight  of  the  brain. 
2^  =  specific  gravity  of  the  entire  brain. 
g  =  specific  gravity  of  the  grey  tissue. 
to  =  specific  gravity  of  the  white  tissue. 

Applying  this  formula  to  the  data  given  above,  namely  : 

P  =  1358;  j>  =  l-037;  g-im2 ;  ic=l-OU  ;  then  =  757-3, 
equal  to  55  per  cent,  of  white  tissue  and  45  per  cent,  of  grey 
tissue  in  the  entire  l)rain. 

About  two  years  ago  I  had  the  happiness  of  conversing  on  this 
matter  with  the  late  Mr.  C.  W.  Merrifield,  a  gentleman  of  great 
scientific  attainments,  and  of  clear  and  powerful  mathematical 
intellect,  whose  recent  death  the  State,  the  scientific  community, 
his  family,  and  his  personal  friends  have  great  reason  to  deplore. 
He  took  an  immediate  interest  in  the  question,  and  embodied 
the  result  of  his  deliberations  on  it  in  a  memorandum,  which  I  am 
glad  to  be  able  to  record  in  this  place.    He  wrote  to  me  : 

'  Your  joroblem  is  exactly  the  same  as  that  of  the  estimation  of 
gold  in  auriferous  quartz.  If  for  gold  you  read  white  cerebral 
tissue,  and  for  silica,  grey  matter,  the  formula  solves  your 




'  Let  g  be  the  specific  gravity  of  the  heavier  substance  (gold) ; 
„  (£  „  „  „        lighter        „  (quartz): 

„  m          „  „  „  mixture; 

a;  be  the  unknown  proportionate  hulk  of  gold  to  a  unit  of 
bulk  of  the  mixture. 

Then  xg  is  the  proportionate  weight  oi  gold,  and  {l—x)q  is  the 
proportionate  weight  of  quartz.  The  sum  of  these  must  give  the 
weight  of  the  mixture,  that  is  — 


or  x(g  —  q)  =  m-  q, 

m  -  q 
or  x  =  


which  gives  the  proportionate  hulk  of  the  gold. 
'  The  proportionate  weight  of  the  gold  is  : 

qx        q  m  —  q 
or  —   ^. 

m        m  g  —q 

Then,  if  ^  =  19,  and  ^  =  2-6,  while  7?z  =  9,  we  have  m-^=6-4, 
q-q  =  \Q'i. 

.  6-4 

Proportionate  bulk  '^fg^^^^^' 

Proportionate  weight  =-^A  x  1?  =  0'824. 

16  "4  9 

'  This  method  gives  very  good  results  when,  as  in  the  case  of 
auriferous  quartz,  the  specific  gravities  are  widely  different, 
because  then  a  small  error  in  the  estimations  of  the  data  does 
not  make  a  large  error  in  the  result.  It  is  otherwise  when  the 
difference  of  density  is  small.    For  instance,  suj)pose — • 

g  =  specific  gravity  white  tissue  =1-035 
2  =    „  „      grey       „  =1-025 

m=    ,,  ,,      brain  altogether  =1-031. 

Then  we  have  for  proportionate  hulk  of  white  tissue  : 

m-g_0-006_Q.g  , 
g-q    0-010  ' 

for  proportionate  iveighf  of  white  tissue  : 

m  g-q  1-031 




'  Now  suppose  the  above  data  to  be  in  error,  so  that  in  reality  : 

(/  =  1-034,  instead  of  1-035 
^7=  1-024,       „  1-025 

m  being  as  before.     Then  -we  have  for 

Bulk  ^1^=^  =  0-7; 

g-q  0-010 

Weight  I-        =  0 -7  X         =  0-70204, 
m  g-q  1-031 

which  is  a  very  different  result,  an  error  of  1  per  cent,  in  the  two 
specific  gravities,  and  both  in  the  same  direction,  altering  the 
result  in  the  ratio  of  6  :  7.' 

Another  method  for  the  quantation  of  grey  and  white  matter, 
recently  proposed,  is  based  upon  the  difference  in  the  quantity  of 
water  contained  in  the  two  tissues,  and  expelled  at  95°.  We 
have  seen  that  grey  tissue  loses  85-27  per  cent,  while  white  tissue 
70-23  per  cent,  of  water.  Now,  if  the  loss  of  water  of  the  entire 
brain  be  known,  and  the  foregoing  data  be  physiological  constants 
or  specially  ascertained  in  each  case,  the  relative  weights  of  white 
and  grey  tissue  may  be  calculated. 


The  brain  is  weighed  in  its  membranes  ;  the  latter  are  then 
carefully  removed  and  weighed,  and  their  weight  is  deducted 
from  the  weight  of  the  brain  previousl}^  found.  The  membranes 
of  a  human  brain  will  be  found  to  weigh  about  60  g.  The  brain- 
tissue  is  then  cut,  or  minced  in  a  machine,  and  steeped  in  alcohol 
until  it  has  become  hard.  It  is  then  worked  through  a  sieve  in 
the  manner  described  in  the  second  chapter  of  this  treatise.  The 
brain-pulp  is  now  exhausted  with  sj^irit  of  85  per  cent,  strength. 
The  boiling  with  spirit  must  be  repeated  until  a  litre  of  spirit 
boiled  with  the  whole  of  the  residue,  filteiT-d  and  distilled  to  dry- 
ness, leaves  only  an  inappreciable  residue.  The  first  spirit-extracts 
which  deposit  the  particular  white  matter  are  kept  separate.  All 
particles  of  brain-tissue  on  the  one  hand  and  all  portions  of  liquid 
on  the  other  must  be  constantly  collected  with  scrupulous  care.  A 
human  brain  will  leave  from  100  to  120  g.  of  dry  albuminous  matter. 

The  alcoholic  solutions  of  the  first  extractions  deposit  on  cool- 
ing and  standing  the  ichite  matter,  which  amounts  to  4-7  to  5  per 



cent,  of  the  mixed  brain-tissues,  but  is  mainly  derived  from  the 
white  tissue.  (Compare  on  this  subject  the  special  analyses  of 
white  and  grey  tissue  given  in  the  previous  chapter.) 

Analysis  of  the  White  Matter. — It  is  exhausted  with  ether,  by 
being  shaken  with  it  in  a  stoppered  cylinder,  and  allowed  to 
settle  ;  the  ether  is  drawn  off  with  a  syphon  worked  by  air-pres- 
sure. The  white  cerebrin  mixture,  containing  the  cerebrin  and 
some  phosphorised  matters,  remains  insoluble,  while  all  kephalin, 
lecithin,  some  myelin,  all  cholesterin,  and  some  other  neutral 
matters,  an  oil  or  ether  (cerebrol)  and  a  yellow  coloured  matter, 
dissolve.    Thus  we  have  : 

in  ether. 

Kephalin,  part  combined  - 

Lecithin,  ,, 



Neutral  (new)  matter 


Yellow  coloured  matter  - 

All  extracted. 

All  „ 

All  „ 

Part  .,  (Phrenosterin). 

All  ;, 

All  .„ 

Treatment  of  the  Ether  Solution  ;  separation  of  its  Ingredients  from 
each  other. — The  ether  is  distilled  off,  the  liquid  residue  is  mixed 
with  an  alcoholic  solution  of  acetate  of  lead  and  excess  of  alcohol, 
and  boiled  for  some  time  under  a  reflux  cooler.  It  is  then  allowed 
to  cool  and  stand.  The  cholesterin  crystallises  in  the  upper  layer 
of  the  mixture,  while  the  kephalin  lead  and  myelin  lead  remain 
below,  insoluble.  The  mixture  is  gently  warmed  until  cholesterin 
is  dissolved,  and  again  allowed  to  cool.  This  process  is  repeated 
to  cause  the  kephalin  lead  and  the  myelin  lead  to  become  as  ad- 
herent and  lumpy  as  possible,  so  that  when  the  warm  spirit  solu- 
tion is  filtered  off  through  a  filter  on  a  hot  funnel,  only  a  minimum 
of  the  insoluble  compounds  may  pass  on  to  the  filter.  The  residue 
is  then  exhausted  with  spirit  by  repeated  long  boiling  with  it. 
Thus  we  have : 

Insoluble  in 
boiling  spirit. 

Soluble  in 
boiling  spirit 

Kephalin  lead 
Myelin  lead 
Myelin  lead 
Lecithin  - 
Cerebrol  - 

All  precipitated. 

Greater  part  precipitated. 





I  Yellow  coloured  matter  All. 
i  Neutral  new  matter  -  All. 



Treatment  of  the  insoluble  in  boiling  Spirit  part  (of  the  Ether  Extract 
boiled  ivith  Lead  Acetate). — This  contains  all  kephalin  lead,  and 
some  'myelin  lead,  which  have  to  be  separated.  This  is  done  by 
absolute  ether,  in  which  kephalin  lead  dissolves  with  a  red  colour, 
while  Mi/elin  lead  remains  as  an  insoluble  white  deposit.  The  latter 
is  Avashed  with  ether  by  decantation  mainly  (with  the  aid  of  a 
syphon  and  air-pressure),  lastly  on  the  filter,  dried  and  weighed. 
The  datum  is  myelin  lead  part  the  first.  The  kephalin  lead  solution 
and  all  ether  used  for  washing  myelin  lead  is  distilled  to  dryness 
and  the  residue  weighed.  It  constitutes  kephalin  lead,  and  con- 
tains all  the  kephalin  which  had  been  present  in  the  white 

In  each,  myelin  lead  and  kephalin  lead,  the  metal  and  phos- 
phorus are  ascertained  by  analysis,  and  from  the  data  the  amounts 
of  pure  myelin  and  pure  kephalin  relatively  are  calculated. 

Treatment  of  the  soluble  in  Spirit  part. — The  boiling  solution  is 
mixed  with  as  much  boiling  water  as  it  will  bear  without  be- 
coming precipitated,  and  is  allowed  to  cool  slowly.  Cholesterin 
(and  phrenosterin  crystaUises  almost  completely  somewhat 
later,  and  covering  the  latter  settles  the  myelin  lead.  Lecithin 
(?  lead),  cerebrol,  yellow-coloured  matter,  neutral  new  matters 
remain  in  solution.    (This  mixture  requires  further  study.) 

Separation  of  Cholesterin  from  Myelin  Lead. — The  isolated  crystal- 
lised matter  is  pressed,  dried,  and  placed  in  absolute  ether  in  a  tall 
stoppered  cylinder,  and  frequently  agitated.  Cholesterin  dis- 
solves, while  the  lead  salt  of  myelin  and  a  cerebroside  settle  as  a 
white  deposit.  The  extraction  of  cholesterin  is  completed  by  the 
repeated  application  of  large  volumes  of  ether.  The  united  ether 
solutions  are  distilled  to  dryness  ;  the  residue  is  dissolved  in  boil- 
ing dilute  spirit  (if  not  sufficiently  dilute,  the  boiling  solution 
must  be  mixed  with  boiling  water  until  it  becomes  turbid),  and 
the  solution  set  to  crystallise.  The  cholesterin  is  filtered  off, 
dried,  and  weighed.  The  white  salt  which  the  ether  dissolving 
the  cholesterin  has  left  insoluble,  is  myelin  lead,  and  a  cere- 
broside. This  is  dried  and  weighed.  It  gives  the  purple  reaction 
with  oil  of  vitriol  alone  on  standing,  immediately  with  sugar- 

The  spirit  mother-liquor  of  the  cholesterin,  after  concentration, 
may  yet  yield  a  minute  quantity  of  cholesterin,  but  does  not  con- 
tain much  else,  colouring-matter  excepted.    It  may  be  added  to 



the  principal  mother-liquor,  from  which  cholesterin  and  myelin 
lead  were  originally  deposited. 

Solution  in  Spirit  of  Lecithin,  Cerebrol,  Yelloiv  Colouring  Matter, 
Neutral  Matter,  and  some  Cholesterin. — Lecithin  does  not  remain 
combined  with  lead  in  watery  spirit.  It  cannot  be  separated 
from  the  rest  of  cholesterin  except  by  precipitant  reagents,  or 
by  chemolysis,  by  which  it  is  decomposed.  Its  quantation  has 
been  found  to  be  effected  with  the  greatest  approximation  to 
truth  by  the  following  process  :  The  spirit  solution  containing 
the  matter  just  named  is  heated  until  all  the  spirit  is  evaporated. 
The  residue  is  then  treated  with  boiling  water,  in  which  it  hardens 
and  becomes  granular.  (In  cold  water  it  swells  and  becomes 
pasty,  so  that  it  cannot  be  separated  from  its  mother-liquor.) 
The  hot  water  is  now  decanted,  and  replaced  by  new ;  the  mix- 
ture is  allowed  to '  cool,  heated  again  to  make  the  solids  curdle, 
and  the  water  is  again  decanted.  This  is  repeated  until  the  de- 
canted water  is  free  from  lead. 

Chemolysis  of  the  Lecithi7i,  etc.,  Mixture  uiih  Barita. — The  mixture 
as  described  is  now  mixed  with  the  necessary  quantity  of  barita 
hydrate  and  water,  and  chemolysed  in  a  closed  platinum  tube 
under  pressure  at  125°  for  at  least  six  hours.  The  contents  of 
the  tube  are  extracted  firstly  with  hot  water,  which  removes 
excess  barita,  ghjcerophosphate  of  harium  and  neurin.  The  solution 
is  neutralised  with  carbonic  acid,  and  the  filtrate  is  evaporated. 
When  suitably  concentrated,  the  addition  of  absolute  alcohol  to 
it  precipitates  all  harium  glycerophosphate,  while  the  filtrate  con- 
tains all  neurin.  The  solution  is  neutralised  by  hydrochloric  acid 
in  excess,  and  the  addition  to  it  of  alcoholic  platinic  chloride 
precipitates  all  neurin  as  platino-chloride  hydrochlorate.  Both 
salts,  the  barium  glycerophosphate  and  neurin  double  salt,  are 
dried  and  weighed. 

Products  of  the  Barita  Chemolysis  of  the  Lecithin  Mixture  which 
are  LnsoluUe  in  Water. — These  are  extracted  with  boiling  spirit. 
The  concentrated  spirit  solution  deposits  yet  some  cholestsrin 
and  a  small  quantity  of  a  barium  salt.  These  are  removed  by 
the  filter.  The  cholesterin  is  separated  from  the  barium  salt 
by  ether.  The  spirit  solution  now  retains  the  bodies  above 
mentioned — namely,  two  neutral  crystallised  bodies  (which  are 
here  noticed  for  the  first  time),  and  perhaps  some  cerebrol  and 
yellow  colouring-matter.    The  two  new  bodies  crystallise  out  of 


the  absolute  alcohol  solution.  Ether  sej^arates  the  second  crys- 
tallised body  from  the  first;  the  latter  is  recrystallised  from 
spirit.  A  thick  mother-liquor  remains,  which  requires  further 
qualitative  examination.  It  is  dried  and  weighed,  and  placed  in 
the  account  as  last  ]^)roduct  of  chemolysis  of  lecithin  mixture. 

That  part  of  the  product  of  the  chemolysis  of  the  lecithin 
mixture  which  is  insoluble  in  water  as  well  as  boiling  spirit 
contains  the  hariim  salts  of  the  fatty  acids  produced  from  the 
chemolysed  lecithin,  as  well  as  from  the  chemolysed  ethylic  ethers 
of  fatty  acids  resulting  from  a  previous  partial  decomposition  of 
lecithin  under  the  influence  of  heat  and  alcohol  only.  As  they 
contain  barium  carbonate,  they  have  to  be  reconstituted  in  a  pure 
state,  and  the  diff'erent  fatty  acids  have  then  to  be  separated. 
This  is  best  done  by  decomposing  the  salts  in  water  with  hydro- 
chloric acid,  and  extracting  the  fatty  acids  with  ether.  The  ether 
is  distilled  off,  the  fatty  acids  are  dissolved  in  watery  ammonia, 
and  precipitated  as  lead  salts  by  lead  acetate.  The  lead  salts  are 
dried,  powdered,  and  exhausted  with  ether.  The  ether  solution 
on  distillation  leaves  lead  oleate,  while  the  salt  insoluble  in  ether 
will  be  found  to  be  mainly  lead  imlmitate  or  mar  gar  ate ,  with  only 
little,  if  any,  stearate.  From  the  oleate  and  palmitate,  with  the 
aid  of  the  neurin  and  glycerophosphate,  the  amount  of  lecithin 
originally  present  is  easily  calculated. 

Treatment  of  the  Alcoholic  Solution  which  has  deposited  the  White 
Matter. — This  solution,  and  all  alcoholic  extracts  of  the  albu- 
minous part  obtained  until  it  is  exhausted,  are  distilled  together 
to  a  convenient  state  of  concentration,  and  allowed  to  cool.  A 
matter  is  then  deposited  which,  from  its  consistency,  has  been 
called  '  huttery,  and  which  consists  of  cholesterin,  lecithin,  kephalin, 
myelin,  and  some  other  ingredients.  This  is  separated  from  the 
liquid  by  filtration,  and  analysed  as  will  be  described. 

Treatment  of  the  Concentrated  Alcoholic  Solution  ivhich  has  deposited 
the  Buttery  Matter. — This  solution  is  evaporated  on  the  water-bath 
until  all  alcohol  has  disappeared.  The  last  portions  of  phos- 
phorised  matters  and  cholesterin,  together  with  small  quantities 
of  oily  ethers,  then  float  on  the  watery  liquid  and  adhere  to  the 
cvaporating-dish.  This  product  is  termed  the  Uast  oily.'  It  is 
most  advisable  to  separate  this  from  the  watery  solution  without 
the  employment  of  a  filter,  and  after  slightly  rinsing  with  dis- 
tilled water,  to  add  it  to  the  Inittery  matter  for  further  analysis. 



Anahjsis  of  the  United  Buttery  and  Last  Oily  Matters. — To  these 
matters,  after  they  have  been  dissolved  in  a  sufficiency  of  hot 
alcohol,  the  lead  process,  as  described  in  the  paragraph  relating 
to  the  ether  extract  of  the  white  matter,  may  at  once  be  api)lied. 
Kephalin  lead  and  myelin  lead  are  precipitated  ;  lecithin,  cho- 
lesterin, and  some  myelin  lead  remain  in  solution,  together  with 
other  matters  to  be  described.    Thus  we  have — 

Precipitated  from  and  insoluble  J  Kephalin  lead  (all). 

The  hephalin  lead,  and  myelin  lead  are  separated  from  each  other 
by  ether  as  above  described,  and  their  quantities  weighed.  The 
lead  contained  in  the  respective  preparations  is  ascertained  by  a 
special  quantation  of  the  phosphorus  and  the  lead,  and  from  these 
data  the  actual  amount  of  each  of  the  free  phosphorised  principles 
is  calculated. 

The  myelin  lead  and  cholesterin  deposited  from  the  hot  alcohol 
are  also  separated  by  ether,  and  the  products  weighed.  The 
cholesterin  may  be  weighed  as  residue  from  the  ether  solution 
after  distillation  of  the  ether  from  a  tared  flask,  or  it  may  be  re- 
crystallised  from  very  dilute  spirit,  and  weighed  in  the  crystallised 
state.  AVhen  thus  recrystallised,  it  is  so  pure  that  its  melting- 
point  is  mostly  at  145°. 

The  cold  spirit  sohdion,  containing  lecithin,  cerebrol,  yellow 
matter,  neutral  new  matter,  and  mostly  a  residue  of  cholesterin, 
together  with  some  lead  acetate,  has  now  to  be  chemolysed,  so 
that  its  ingredients  can  be  ascertained  from  the  products  of  de- 
composition. The  spirit  is  first  evaporated,  and  the  residue 
heated  with  water,  which  dissolves  the  acetate  of  lead  and  any 
impurity  soluble  in  water.  This  purification  with  hot  water  (cold 
water  has  to  be  avoided,  as  it  makes  the  residue  swell  and  pre- 
sent a  semi-mucilaginous  state)  is  repeated  until  the  water  is  free 
from  lead.    The  residue  is  now  treated  as  follows  : 

Chemolysls  of  the  Last  Residue  of  the  Buttery  and  Last  Oily  Matter 

in  boiling  spirit  - 

Soluble  in  boiling  spirit,  part 
deposited  on  cooling 

Cholesterin  j  deposi 

Myelin  lead  >■  on 

and  a  cerebroside  I  cooling. 
Yellow  matter. 
Neutral  matters. 


2uhicJi  ivas  not  precipitated  hy  Lead  Acetate. — The  necessity  for  this 
process  arises  from  the  fact  that  the  bulk  of  the  lecithin  cannot 
be  separated  from  the  last  traces  of  cholesterin  and  from  the 
small  quantities  of  ether  formed  during  the  long  processes 
with  alcohol.  There  are,  moreover,  matters  present,  such  as 
the  neutral  new  matters,  which  are  all  soluble  in  ether  as  well 
as  alcohol,  and  do  not  combine  with  reagents  in  such  a  manner 
as  to  become  insoluble  while  the  other  bodies  remain  soluble,  or 

The  mixture  as  described  is  chemolysed  in  the  same  manner  as 
the  residual  mixture  from  the  lead-precipitates  from  the  ether- 
extract  of  white  matter  described  above.  It  is  mixed  with  the 
necessary  quantity  of  barita  hydrate  and  water,  and  heated  in  a 
closed  platinum-tube  under  pressure  at  1^5°  for  at  least  six  hours. 
It  may  also  be  boiled  in  an  open  platinum  dish,  with  frequent  re- 
newal of  the  water,  for  at  least  twelve  hours  ;  but  the  process  is 
liable  not  to  be  complete,  as  the  fatty  acid  salts  formed  may 
enclose  portions  of  lecithin  and  protect  them  from  the  influence 
of  the  barita.  Smaller  quantities  of  matter  may  be  enclosed  in 
glass  tubes  and  sealed,  and  then  heated  to  125°,  surrounded  by 
water  in  a  closed  brass  tube.  This  last  precaution  is  necessitated 
by  the  fragility  of  the  glass,  if  unprotected.  The  employment  of 
the  platinum  tube  is  preferable,  owing  to  its  simplicity.  The 
contents  of  the  tube  are  extracted  with  hot  water,  which  removes 
excess  of  baiita,  ghjceropJiosj^hate  of  barium  and  neurin.  These  are 
isolated  as  above  described — the  glycerophosphate  by  alcohol, 
and  the  neurin  by  platinic  chloride. 

The  remaining  solid  products  of  the  chemolysis,  which  are  in- 
soluble in  water,  are  extracted  with  boiling  spirit.  In  this  all 
cholesterin,  and  other  matters  not  yet  fully  identified,  and  a 
little  barium  salt  of  a  fatty  acid  dissolve,  while  the  barium  salt 
of  the  fatty  acids  produced  by  the  chemolysis  from  lecithin  and 
cerebrol  remain  insoluble. 

The  spirit  solution,  when  sufficiently  watery,  deposits  all  cho- 
lesterin, which  is  dried  and  weighed  ;  it  retains  in  solution  the 
neutral  matters  alluded  to.  This  last  mother-liquor  is  evaporated 
to  dryness  and  weighed,  and  the  product  is  entered  into  the 
record  of  the  analysis  as  crystallisable  undetermined  products. 

The  harium  scdls  of  the  fatty  acids,  oleate  and  margarate  or  pal- 
mitate,  are  decomposed  with  hydrochloric  acid  and  water  under 



ether,  and  the  h'beratecl  fatty  acids  are  then  combined,  first  with 
ammonia,  next  with  lead.  From  the  dry  mixture  of  lead  oleate 
and  margarate  the  former  is  extracted  by  ether.  The  margarate 
remains  as  a  white  substance,  which  is  easily  weighed ;  the  oUate 
is  best  weighed  as  residue  of  the  ether  solution  distilled  from  a 
tared  flask. 

In  calculating  the  amount  of  lecithin  from  the  oleic  and  margaric 
acids  obtained  as  lead-salts,  and  comparing  these  data  with  those 
obtained  by  calculation  from  the  quantities  of  glycerophosphoric 
acid  and  neurin,  the  following  circumstances  have  to  be  borne  in 
mind : 

Of  the  lecithin  present  in  the  brain,  and  extracted  by  the 
alcohol,  a  part  is  already  decomposed  during  the  chemical  opera- 
tion. AYe  shall  see  below  how  an  excellent  (juantatloii  of  the 
lecithin  can  be  made  upon  any  portion  of  brain,  provided  it  is  not 
intended  to  estimate  many  other  or  all  the  ingredients  of  the 
extract  obtained  therefrom.  But  in  the  course  of  a  complete 
analysis  of  a  single  brain,  such  as  is  here  described,  the  complete 
quantation  of  the  lecithin  as  such  is  not  feasible,  on  account  of 
the  decomposition  just  alluded  to.  This  decomposition  causes  a 
loss  of  neurin  and  glycerophosphoric  acid  on  the  one  hand,  which 
remains  in  the  watery  mother-liquor  containing  the  principles  of 
the  brain  soluble  in  water,  and  a  loss  of  fatty  acids  on  the  other, 
which  combine  with  alcohol  and  form  ethers.  These  ethers  are, 
of  course,  again  decomposed  during  the  barita  chemolysis,  so  that 
ultimately  the  whole  of  the  fatty  acids  which  were  present  in  the 
form  of  lecithin  are  obtained  as  barium  salts.  It  follows,  there- 
fore, that  when  the  quantities  of  fatty  acids  found  are  compared 
with  the  quantities  of  neurin  and  glycerophosphoric  acid,  equiva- 
lent for  equivalent,  there  will  be  an  excess  of  fatty  acid  over  the 
neurin  and  glycerophosjDhoric  acid.  It  is  therefore  necessary  to 
take  the  fatty  acids  as  the  basis  of  calculation  for  the  amounts  of 
lecithin  present  in  the  original  extract,  and  the  neurin  and 
glycerophosphoric  acid  only  as  subsidiary  aids  for  the  determina- 
tion of  the  minimum  and  the  control  against  accident. 

Separation  of  the  Ingredients  of  the  Buttery  Matter  by  a  Process  in 
which  Caustic  Barita  is  em^jloyed. — In  this  process  barita  takes  the 
place  of  lead  which  is  employed  in  the  process  just  described. 
The  results  are  in  the  main  analogous.  The  mother-liquors  will 
have  to  be  chemolysed  with  more  barita,  as  in  the  previous  case, 


but  the  process  will  not  be  delayed  by  the  necessity  of  removing 
the  excess  of  lead  acetate. 

The  buttery  matter  is  dissolved  in  a  sufficient  quantity  of  hot 
spirit,  and  filtered  hot.  To  the  hot  solution,  hot  barita  water 
(saturated  in  the  cold)  is  now  added,  while  the  mixture  is  kept 
boiling.  A  precipitate  separates  and  becomes  adhesive.  The 
solution  is  decanted  and  filtered  boiling.  The  precipitate  which 
remains  insoluble  is  exhausted  with  boiling  spirit,  dried  and 
treated  with  ether.  KephaUn-harium  goes  into  solution,  while  a 
white  salt  {myelin-barium  and  small  quantities  of  barium  salts  of 
fatty  acids)  remains  insoluble.  The  hot  spirit  solution,  on  cooling, 
deposits  a  white  precipitate,  and  then  is  almost  free  from  ingre- 
dients. The  precipitate  is  isolated,  dried,  and  exhausted  with 
ether.  This  solution  of  ether  contains  all  cholesterin,  and  a 
mere  vestige  of  kephalin.  The  white  precipitate  contains,  firstly, 
a  body  soluble  in  boiling  spirit,  and  deposited  from  it  in  needles 
(curved  needle  body),  and  a  body  which  is  now,  after  removal 
of  the  bodies  soluble  in  ether,  insoluble  in  boiling  spirit,  and 
contains  much  barium  and  phosphorus. 

The  kephalin-hamm  as  precipitated  from  human  buttery  by 
barita-water  in  the  abov^e  process  is  not  yet  a  pure  compound,  as 
was  shown  by  the  following  tests  of  a  specimen.  It  was  insoluble 
in  boiling  spirit,  easily  soluble  in  ether,  twice  precipitated  by 
absolute  alcohol,  and  dried  over  oil  of  vitriol  at  70°.  It  contained 
2.3 '30  per  cent.  Ba.  and  4  67  per  cent.  P. 

The  amount  of  barium  found  corresponds  approximately  to  a 
dibarium  kephalin,  which  requires  24-77  per  cent.  Ba.  But  the 
amount  of  phosphorus  is  in  excess  of  that  theory,  which  requires 
2  '9  per  cent.  P,  and  must  be  left  unexplained.  Dibarium-kephalin 
has  an  analogue  in  a  diplumbic  kephalin,  which  I  have  described 
in  the  chapter  relating  to  kephalin. 

Analysis  of  the  Cerehrin  Mature. — This  mixture  consists  of  a 
number  of  well-defined  immediate  principles,  which  belong  mainly 
to  three  distinct  categories. 

(1.)  Cerehrositles  or  bodies  of  the  glucoside  type,  which  contain 
as  constitutional  base  a  peculiar  sugar,  cerehrose.  The  type  of 
these  bodies,  pthrenosin,  forms  the  main  quantity  of  the  ingredients 
of  the  mixture.  It  is  insoluble  in  cold  absolute  alcohol.  Keratin 
is  soluble  in  much  cold  absolute  alcohol,  at  least  for  some  time, 
and  is  deposited  slowly  on  standing  in  a  semi-crystalline  form. 



A  body  crystallising  apparently  in  curved  needles,  bregenin,  is 
permanently  soluble  in  alcohol.  These  bodies  do  not  combine 
with  lead  when  it  is  added  as  acetate  to  their  solution  in  spirit. 
But  there  are  a  number  of  cerebrosides  which  do  combine  with 
lead  when  it  is  added  as  acetate  to  their  spirit  solution  :  of  this 
class  is  cerebrinic  acid,  and  spherocerehrin,  and  the  three  bodies 
accompanying  spherocerebrin  as  described  in  the  article  on  the 

(2.)  Fhosphorised  bodies,  which,  owing  to  some  of  the  fatty 
acids  contained  in  them  being  identical  with  or  nearly  allied  to 
the  fatty  acids  contained  in  the  cerebrosides,  have  the  same  or 
very  nearly  the  same  solubility  in  alcohol  and  other  solvents  as 
the  cerebrosides,  and  therefore  follow  them  pertinaciously : 
sjphingomyelin  and  apomyelin. 

(3.)  Sulphurised  bodies,  of  which  a  preliminary  description  has 
been  given  in  a  previous  chapter. 

The  cerebrin-mixture  also  always  contains  varying  quantities  of 
bases,  particularly  potash  and  soda. 

The  cerebrosides  being  mostly  neutral  bodies,  having  no  affinity 
for  either  acid  or  alkali,  can  be  isolated  with  solvents  only.  Of 
the  cerebrin-mixture  an  elementary  analysis  should  be  made,  and 
its  results  stated  in  atoms  w^ith  sulphur  as  unit,  and  again  with 
phosphorus  as  unit.  This  will  at  once  show  the  proportions  of 
atoms  to  each  other,  and  be  the  chief  control  of  the  processes  of 
quantitative  separation  to  be  undertaken  afterwards. 

The  cerebrin  mixture,  dissolved  in  alcohol,  may  then  be  treated 
with  lead  acetate  and  a  little  ammonia,  and^he  precipitate  may 
be  exhausted  with  boiling  spirit.  This  process  separates  the 
mixture  of  cerebrosides  into  the  two  categories  described  above 
under  (1).  The  sulphurised  bodies  remain  principally  in  the 
lead  precipitate,  the  phosphorised  principles  distribute  themselves 
over  precipitate  and  solution.  The  separation  and  quantation  of 
these  matters  requires  further  study. 

The  nitrogen  in  the  cerebrosides  is  probably  all  present  in  a 
form,  which  by  chemolysis  with  barita  or  sulphuric  acid,  suffi- 
ciently long  continued,  will  appear  as  sphingosin.  Thus  neurin 
on  the  one,  and  sphingosin  on  the  other  hand,  will  probably  be 
the  only  nitrogenised  nuclei  to  be  isolated  by  chemolysis.  They 
are  certainly  the  principal  ones  as  regards  quantity ;  should  the 
sulphurised  bodies  contain  any  nitrogen  and  that  in  a  particular 


form,  then  the  quantity  of  this  particular  product  would  be  much 
below  the  quantities  of  the  products  just  mentioned. 


Of  the  left  hemisj^here,  which  when  entire  weighed  596  g., 
460  g.  were  taken  for  the  following  quantations.  The  tissue  was 
comminuted  and  exhausted  with  boiling  spirit,  etc.,  and  yielded 
the  following  educts  : 

Albuminous  matters  =35 '06  g.,  equal  to  7-62  per  cent,  of 

JVhite  matter,  deposited  from  spirit,  21*93;  the  same  after  ex- 
traction with  cold  ether  (cerebrin-mixture)  dry  =  12  "28  g.  Soluble 
in  ether,  9*65  g.  These  cerebrosides,  etc.,  boiled  with  absolute 
alcohol,  gave — 

(a.)  Less  soluble  cerebrins,  phrenosin,  etc.,  deposited  imme- 
diately 8-11  g. 

(b.)  More  soluble  ones,  kerasin,  etc.,  deposited  after  days  0*56  g. 
And  left  insoluble  stearoconote,  albumen,  and  paper  fibres  0'78  g. 

Of  this  last  item  0*53  were  soluble,  0*25  insoluble  in  hot  benzol. 
The  insoluble  in  benzol  part  contained  a  body  which  left  a  black 
ash  on  combustion,  and  contained  much  phosphorus.  It  was  an 
earthy  compound  of  a  phosphorised  body.  It  gave  a  brownish 
red,  but  no  genuine  oleo-cholide  reaction. 

The  alcoholic  solution  from  the  cerebrins  =  340  cc.  was  divided  in 
two  equal  halves  of  170  cc.  each.  To  one  half  platinic  chloride 
was  added  as  long  as  a  precipitate  was  produced.  The  precipitate, 
containing  a  phosphorised  body,  weighed  0*85  g.,  and  contained 
9-58  per  cent.  Pt ;  it  yielded  further  3*13  per  cent.  P.  To  the 
second  half  of  the  alcohol  solution  cadmic  chloride  was  added, 
and  the  precipitate  obtained  weighed  0-8124  g.  ;  it  yielded 
13*27  per  cent.  Cd  and  3*42  per  cent.  P. 

Of  the  matters  dissolved  in  spirit,  and  not  precipitated  by  these 
alkaloid  reagents,  0*3619  g.  were  yet  precipitated  by  water. 

The  ether-extract  from  the  cerebrln  mixture  weighed  9*65  g. 

The  butter//  matter,  soluble  entirely  in  cold  ether  =21*65  g. 

The  last  oihj  matter,  treated  with  lead  acetate,  yielded  lead  pre- 
cipitates which  together  weighed  11  '8450  g. 

Out  of  these  there  was  obtained  lecithin  =2  8995  g.    (This  was 



easily  soluble  in  cold  absolute  alcohol,  and  gave  the  characteristic 
tests  with  platinic  and  cadmic  chloride.) 

Further  kejjhalin  lead  =  0-8435  g.  =  0*5659  g.  keplialin ;  and 
myelin  lead  =  6*6080  g.  =5*2041  myelin. 

The  last  watery  extract  gave  a  phosphomolybdate  precipitate  of 
alkaloids,  which  weighed  dry  3*7084  g.  It  yielded  further  1  *56  g. 
zinc  lactate  dried  in  vacuo  over  oil  of  vitriol  =1*0074  g.  pure 
sarcolactic  acid. 

The  inosite  amounted  to  2*5335  g. 

The  undefined  organic  extractives  weighed  2*7822  g. 

The  scdts,  as  carbonates,  weighed  1*7218  g.  Of  these  0*39  were 
potassium  =0*745  KCl,  and  0-39  sodium  =0*9844  NaCl.  The 
salts  as  chlorides  weighed  1*7294  g.,  and  out  of  this  mixture 
2-4610  g.  PtCl4(KCl)2  were  obtained. 

In  the  calculation  of  kephalin,  myelin,  and  lactic  acid,  the 
following  formulae  were  used,  which  should  be  considered  as 
provisional,  and  will  have  to  be  tested  by  further,  or  supple- 
mented by  direct  analysis  of  the  products  : 

Kephalin,  rnolec.  weight  =  836  ;  kephalin  lead  =C42H^5NPOj3Pb2 
M.W.  =1246. 

Myelin, M. W.  =  760 ;  myelin  lead  =  C^oH.gPbNPOio,  M.  W.  =  965. 
Sarcolactic  acid  CgHgOg,  M.W.  =  90. 

Zinc  sarcolactate  dihydrate,  CqE^qZuO^  +,  M.W.  =  279. 

The  buttery  matter  which  had  been  soluble  in  ether  (21*6450  g.) 
was  boiled  with  barita  and  yielded  6*7  g.  of  cholesterin,  .^ith 
16*5  g.  of  barium  salts  of  fatty  acids.  .  The  latter  contained  oleate 
(as  shown  by  the  oleo-cholide  reaction),  much  phosphorus,  and  a 
small  quantity  of  a  body  which  was  soluble  in  ether.  But  the 
complete  extraction  with  ether  was  impracticable,  as  the  turbid 
liquid  would  neither  settle  nor  allow  itself  to  be  filtered.  This 
difficulty  is  not  rarely  met  with  when  dry  barium  or  lead  salts 
of  brain  educts  are  subjected  to  ether  treatment  for  the  extraction 
of  some  ingredient. 

The  ether  extract  from  the  cerebrin  mixture,  containing  the 
kephalin  and  cholesterin,  was  treated  with  alcoholic  lead  acetate 
and  filtered  boiling.  The  insoluble  residue  of  kephalin  lead 
weighed  2*6410  g.,  which,  assumed  to  contain  2Pb,  is  equal  to 
1772  g.  free  kephalin. 

The  solution  in  spirit  of  the  cholesterin,  etc.,  was  evaporated,  and 
the  residue  freed  from  lead  acetate  by  hot  water.    The  cholesterin 


was  then  re-crystallised  and  weighed.  When  the  cholesterin  thus 
obtained  was  re-dissolved  in  ether,  a  white  matter  remained  in- 
soluble, weighing  0-2680  g.,  and  being  entirely  combustible  on 
platinum  foil. 

Quantation  of  the  Ingredients  of  the  Eight  Hemisphere. 

The  total  hemisphere^  with  the  membranes,  weighed  589  g.  ; 
after  removal  of  membranes,  564  g.  ;  of  this  quantity,  465  g.  were 
employed  in  the  following  quantations  : 

The  albuminous  substance  amounted  to  35-68  g.,  equal  to  7-66 
per  cent,  of  the  hemisphere  tissue. 

The  ivhite  matter  deposited  from  spirit  dry  was  =  18'60  g. 

The  ether-extract  from  this     6-97  g. 

The  cerebrins  insoluble  in  ether     11-63  g. 

The  buttery  matter  (=  21-66  g.)  in  alcohol  was  treated  with  lead 
acetate,  and  boiled.  The  precipitates  insoluble  in  boiling  alcohol 
were  suspended  in  ether  for  separation,  but  the  cylinder  containing 
the  mixture  breaking  spontaneously,  the  quantation  was  lost.  In 
the  table  this  void  is  filled  up  by  data  obtained  from  the  data 
concerning  the  left  hemisphere  by  calculation. 

Tlie  inosite  was  obtained  in  two  portions,  one  with  neutral 
acetate  (it  was  not  previously  known  that  inosite  was  so  preci- 
pitated), another  with  basic,  together  about  0*43  g.  The  lead 
having  been  removed  from  the  liquid  with  sulphuric  acid,  the 
lactic  acid  was  extracted  ^and  formed  into  zinc  salt.  It  weighed, 
dry  at  100°,  0*87  g.  =0-64  sarkolactic  acid. 

Alkaloids  were  precipitated  from  the  mother-liquor  by  phospho- 
molybdic  acid.  The  precipitate  Aveighed  3  8  g.,  and  contained 
1  -30  g.  mixed  alkaloids. 

The  mother-liquor  was  treated  with  barita,  etc.,  evaporated, 
and  the  residue  burnt.  The  indefinite  extractives  amounted  to 
2-63  g. 

Of  lootassium  0-25  g.,  of  sodium  0*40  g.,  were  obtained. 

The  hot  mother-liquor  of  the  buttery  matter  treated  with  lead 
acetate  (of  which  operation  the  insoluble  precipitates  were  lost  as 
above  described),  on  cooling  deposited  myelin  lead  and  cholesterin, 
weighing,  when  dry,  6-99  g.    The  myelin  weighed  5*22  g. 

The  spirit  filtrate,  containing  lecithin  and  little  cholesterin,  after 
evaporation,  left  a  residue  weighing  8*13  g. 

The  remaining  bodies  containing  cholesterin  were  chemolysed 



with  barita,  and  gave  cJioIesterin  =  8-93  g.  pure,  and  8-80  g.  harkim 
salts  of  fatty  acids. 

Quantation  of  the  Ingredients  of  the  Cerehellum. 

The  total  weight  of  the  fresh  cerebellum  with  membranes  was 
135  g.j  and  after  removal  of  membranes,  etc.,  124  g.  were  analysed. 

The  albuminous  matter  amounted  to  11-3809  g.  =  9-17  per  cent, 
of  cerebellum. 

The  ivhite  matter  from  first  spirit  was  =  1  "81  g.  Of  this,  0*2185  g. 
were  soluble,  1*6645  g.  insoluble  in  ether  =cerebrins. 

The  filtrate  from  the  ivhite  matter  was  evaporated  and  treated 
directly  with  lead  acetate.  There  were  obtained  kephalin  lead 
=  1*97  g.  ;  myelin  lead  1*65  g.  ;  in  the  solution,  cholesterin 
with  lecithin  and  myelin  lead  =3*26  g.  j  a  second  portion  of 
myelin  lead  with  lead  salt  insoluble  in  ether  containing  inosite 
=  0*05  g.  This  inosite  having  been  precipitated  by  neutral  lead 
acetate  (a  reaction  hitherto  unknown)  made  the  quantation  of 
this  body  inaccurate.  It  amounted  probably  to  0*66  g.  for  the 
entire  cerebellum. 

The  lactate  of  zinc,  dry  at  100°,  weighed  019,  equal  to  0*1352  g. 
sarkolactic  acid. 

21ie  alkaloids,  precipitated  by  phosphomolybdic  acid,  weighed  in 
combination  1-62  g.,  free  0*6920  g. 

The  extractives,  mixed  with  the  salts,  weighed  1*55  g. 

The  alkali  salts  consisted  of  0*01  potassium  and  0*02  sodium. 

The  mixture  of  cholesterin,  lecithin. and  myelin  lead,  above  de- 
scribed as  weighing  3*26  g.,  was  boiled  with  barita  and  a  little 
spirit  for  three  hours.  The  watery  solution  of  neurin  glycero- 
phosphate and  excess  of  barium  was  separated  from  the  insoluble 
matter.  The  cholesterin  was  extracted  by  boiling  spirit,  and 
weighed  1*95  g.  Its  melting-point  was  145°.  The  barium  scdts  of 
the  fatty  acids  weighed  2-56  g. 

Quantation  of  the  Constituents  of  the  Mesenkephalon. 

The  mesenkephalon  and  medulla  oblongata  weighed  34  g., 
without  the  membranes  33  g. 

The  albumen  amounted  to  2*48  g.  =  7*5  per  cent,  of  the  mesen- 

The  luhite  matter  weighed  0*64  g.  ;  of  this  0*03  were  soluble  in 
ether,  0-56  insoluble. 


The  huttery  matter  yielded  0*67  kephalin  lead. 

The  lactate  of  zinc  weighed  0-11,  air  dry,  equal  to  0*07  lactic  acid. 

The  rest  of  the  matters  soluble  in  water  were  not  estimated  on 
account  of  their  small  quantity. 

The  data  thus  far  ascertained  have  been  arranged  in  the  follow- 
ing table.  Thej^  claim  to  be  minima  only,  and  with  improved 
processes  somewhat  larger  quantities  will  probably  be  found. 
Blanks  are  left  where  the  quantations  could  either  not  be  made, 
or  were  unsatisfactory  when  the  products  were  tested. 

The  experience  gained  by  this  analysis  has  shown  that  the 
division  of  all  the  educts  of  a  brain  into  five  primary  categories 
is  practical.  They  are  (1)  albumen,  (2)  white  matter,  (3)  buttery 
matter,  (4)  last  oily  matter,  (5)  matters  soluble  in  water.  Of 
these,  the  last  oily  and  the  buttery  matters  maj^  be  treated 
together  for  the  separation  of  their  ingredients,  when  the  cere- 
bellum or  mesenkephalon  are  concerned.  When  derived  from 
the  hemispheres  these  products  are  more  conveniently  kept  apart. 

The  table  contains  about  130  data.  But  it  will  be  seen  that 
the  cerebrosides,  e.g.,  occupy  only  one  column  (col,  6),  whereas 
probably  ten  columns  will  be  required  to  register  the  quantities  of 
various  specific  bodies  of  which  the  insoluble  in  ether  part  of  the 
white  matter  is  composed.  I  estimate,  therefore,  that  the  quanti- 
tative analysis  of  one  brain  will  involve  the  production  and 
weighing  of  about  300  definite  bodies  or  compounds.  Each  of 
the  four  divisions  of  the  brain,  and  each  of  the  two  varieties  of 
tissue,  the  white  and  the  grey,  would  thus  require  about  fifty 
quantations  for  chemical  characterisation. 

The  loss  registered  in  the  table  appears  at  first  sight  enormous. 
One  part  was  incurred  by  diffusion  from  the  parts  immersed 
in  water  for  the  estimation  of  the  specific  gravities  as  described 
in  a  previous  chapter.  This  quantity  was  1-65  g.,  as  ascertained 
by  eva2:)oration  of  the  water  and  weighing  of  the  dry  residue.  An 
uncertain  part  of  weight  was  lost  by  evaporation.  But  the 
greatest  part  was  lost  in  the  course  of  the  anatomical  separation 
of  white  and  grey  matter,  in  the  course  of  comminution,  and 
transfer  from  filter  to  filter  and  vessel  to  vessel.  This  loss  may 
be  much  diminished  by  improved  apparatus,  but  in  the  present 
case  it  imports  only  a  slight  degree  of  inaccuracy  into  the  general 
result  of  the  analysis,  as  its  effect  has  been  supplemented  by  a 
proportional  calculation. 



I— I 







CO  ; 

OCiC-l  OO-t^  OOi  T-ll^ 
-tilOO  OO  OO  OO 
OOO        OO       OO  OO 










Indefinite  Extrac- 

C0C0O5  CO-*  COr-H  -tl(M 
CO                      ^."^                                   *?  'P 

'f^JifjAn       OO       OO  OO 


Hypoxanthin  and 

O  CO                                          O         I-H  T-l 

TO  O  CO  11  1  r-l  P  C^' 
Ah        O          '     '           '  O       O  O 


Lactic  Acid. 

^OCO  l-«kO  O-H  OO 
COOi-i       OO       OO  0(M 

Ot-hO        OO       OO  OO 





CO  00  O       CO  -i^        O^             O  QO 
CO  p        O  rH        p  --O        p  p 

OOO       OO       OO  OO 


T— 1 

Cholesterin  Total. 

COOilO  1— iiO  OO  CNCO 
010505  Or— (  COOi  >— 100 
OO'-Oi-t       i-H'M       OO  Oi-I 


T— ( 

Lecithin  Total. 

O  1-^  OO  W  CO  Ol  o 
O     I   O                       O  1^       O  i-H 

o'cN        OO        OO  Or-I 


Myelin  Total. 


Ol  O  to  coco  OJfN  OOS 
OJO^l^        CMr-H        OO  OCO 

lOiCCO       OO       OO  OO 

f— > 


Kephalin  Total. 


1              \a  ^       o  *0  CO 

CO   1  <>i      7*^  p      <?  T'      o  p 

CO       I-H        OO       OO  OO 



Buttery  Matter. 

CO        CO  -h 

CO  p  (>4        1  CO      'r*    1  IT' 
I-H  CO         '  o       o    '         '  ^ 
'M  (N 



TV.   ^vj.,   feDiuuie  1X1 

J^iOOI  COfN  COO  -^lOO 
CiCOOq        O^        coco  OOO 

COOlO        0(M        OO  OrH 



W.  M.  insoluble  in 

CO  OO  CO        CO  CO        f  -H 

to      to                   to    I  1 
Ah  0^  Ah      O          o    1  i 

I-H  I-H 



i  U-S 

vvnite  iviatter. 

OCOCO        --+HOO  l^O 
COOOO        COCi        OlCfJ  Oi-H 

COi-HrH  OCO  OO  O-H 
1—1  (M 




OOCO'*        coo        OO  C050 

CO  o  as      -+11^     QO  lo  o 

lO  K-i  O  Ol  O  CO  O  CO 
CO  CO  rH 

1  o 




OJ  P 
»OCO^        coco        CSCO        CO  CO 

:o  CO  (M      CO  CO         ■  CO 

1          -+I  rH 


1  ^ 


Weights  without 

^  O  Oi  CO 

CO  lOI  CO  1  1  1  '  1  1 
>0  O  I-H                   1             II  II 


Weights  with 

1  as  CO  m  -H 

1  CO  Oi  CO      00   1        j    1  II 



S   »  Ph 



I  have  no  doubt  that  by  continued  stud}^  the  quantitative 
analysis  of  the  brain  may  attain  a  very  high  degree  of  accuracy. 
This  belief  is  based  upon  a  number  of  compounds  and  processes 
described  in  the  chapters  relating  to  the  different  principles,  which 
may  here  be  summarily  referred  to,  although  there  has  not  yet 
been  time  for  giving  them  places  in  a  systematic  analytical 

The  kejjhallns  may  be  combined  with  lead,  barita,  or  cadmium 
chloride.  All  these  compounds  are  soluble  in  ether,  insoluble  in 

The  lecithins  may  be  combined  with  cadmium  chloride.  These 
compounds  are  insoluble  in  ether,  insoluble  in  cold  alcohol, 
soluble  in  boiling  alcohol,  soluble  in  cold  benzol. 

The  myelins  must  be  combined  with  lead ;  in  that  state  they  are 
insoluble  in  alcohol  and  ether,  hot  or  cold. 

The  paraimjelins  may  be  combined  with  cadmium  chloride  ;  in 
that  state  they  are  soluble  in  hot  benzol,  insoluble  in  cold,  in- 
soluble in  ether. 

The  amidomyelins  may  be  combined  with  cadmium  chloride  ;  in 
that  state  they  are  insoluble  in  hot  or  cold  benzol,  and  insoluble 
in  ether. 

The  spiling omyelins  are,  as  cadmium  chloride  salts,  soluble  in 
hot  benzol,  and  soluble  in  much  cold  benzol ;  benzol,  therefore, 
offers  no  facilities  for  their  separation. 

The  assiirins  are  not  precipitated  from  alcohol  by  either  lead 
acetate  or  cadmium  chloride,  but  by  platinic  chloride. 

Phrenosin  and  kerasin  are  soluble  in  boiling  spirit,  insoluble  in 
cold  ;  the  later  deposition  of  kerasin  affords  means  for  its  sei)ara- 
tion.  They  are  insoluble  in  ether,  and  do  not  combine  with  lead, 
or  cadmium  chloride. 

Kriaosiii  is  soluble  in  hot  ether,  insoluble  in  cold  ;  soluble  in 
boiling  alcohol. 

Bregenin  is  soluble  in  cold  ether  and  cold  alcohol.  Neither 
krinosin  nor  bregenin  combines  with  lead,  or  with  cadmium 

The  cerehrinacides  combine  with  lead,  and  as  lead  compounds 
are  insoluble  in  boiling  alcohol ;  a  part  of  the  lead  compounds  is 
.soluble,  another  insoluble  in  benzol. 

Many  of  the  phosphatides  can  also  be  combined,  like  assurin, 



with  platinic  chloride.  If  we  add  to  these  reagents  the  means 
furnished  by  limited  chemolysis,  and  by  complete  chemolysis,  it 
will  be  seen  that  the  quantation  of  any  one  of  the  well  defined 
ingredients  is  now  feasible.  Bat  I  have  no  doubt  that  specific 
solvents,  as  well  as  precipitants,  will  be  found  for  all  the  brain 
educts  or  their  compounds.  Thus  a  few  trials  with  acetone  have 
shown  that  it  will  be  usef  td  in  the  separation  of  the  cerebrosides  ; 
in  a  similar  manner  chloroform  will  be  an  occasionally  useful  sol- 

The  power  of  mercuramin  for  the  removal  of  all  acids  from 
any  solution,  and  their  recovery  from  the  precipitate,  gives  to 
the  analyst  a  power  which  was  undreamed  of  a  few  years  ago. 
The  power  of  phosphomolybdic  and  phosphotungstic  acids  for  the 
isolation  of  alkaloids  has  made  their  extraction  amenable  to  pure 
reagents.  And  we  can  see  from  the  behaviour  of  many  of  the 
educts  with  even  commonplace  reagents  that  amongst  them 
there  are  at  least  some  which  will  furnish  means  for  stoichiometric 

When  the  normal  composition  of  the  brain  shall  be  known  to 
the  uttermost  item,  then  pathology  can  begin  its  search  for 
abnormal  compounds  or  derangements  of  quantities.  Thus  the 
amyloid  degeneration  is  specific  to  brain  and  nerve-tissue,  and 
can  be  considered  hypothetically  as  a  reduction  of  an  ingredient 
of  decomj^osed  cerebrosides.  This  hypothesis  has  the  advantage 
that  it  is  as  yet  the  only  one  which  can  be  made  regarding  this 
remarkable  disease.  I  believe  that  the  great  diseases  of  the 
brain  and  spine,  such  as  general  paralysis,  acute  and  chronic 
mania,  melancholy,  and  others,  will  all  be  shown  to  be  connected 
with  specific  chemical  changes  in  neuroplasm,  the  products  of 
which  cannot  be  more  complicated  than  the  chemolytic  products 
of  the  educts ;  they  need,  however,  not  be  identical  with 
chemolytic  products,  but  may  be  new  morbid  products.  Here  is 
a  field  for  inquiry  of  the  possession  of  which  the  guardians  of 
refuges  for  the  insane  will  hereafter,  I  have  no  doubt,  endeavour 
to  make  good  use. 

The  knowledge  of  the  composition  and  23roperties  of  neuro- 
l^lasm  and  of  its  constituents  will  also  aid  us  in  devising  modes  of 
radical  treatment  in  cases  in  which  at  present  only  tentative 
symptomatic  measures  are  taken.    In  short,  it  is  probable  that  by 



the  aid  of  chemistry  many  derangements  of  the  brain  and  mind, 
which  are  at  present  obscure,  will  become  accurately  definable 
and  amenable  to  precise  treatment,  and  what  is  now  an  object 
of  anxious  empiricism  will  become  one  for  the  proud  exercise  of 
exact  science. 


Acetic  acid,  216. 
Acids  (as  principles),  199. 
^sthesin,  160. 
Albuminous  principles,  211. 
Alcohols,  199. 
Alkaloids,  192,  225. 
Amido-acids,  196. 
Amidokephalin,  104. 
Amidolipotides,  188. 
Amidomyelin,  98,  44. 

„        Preparation  of,  99. 

,,        Properties  of,  102. 
Analysis,  Consideration  of  methods  of, 

Apomyelin,  99. 
Assurin,  120. 

Bregenin,  188. 
Buttery  matter,  31. 

Calcium  acid  glycero-phosphate,  79, 

Caramels,  148,  158,  166,  171,  179. 
Carbohydrates,  199. 
Cerebrinacides,  178. 
Cerebrinic  acid,  179. 
Cerebrose,  143,  170. 
Cerebrosic  acid,  145. 
Cerebrosides,  134,  250. 

„         Separation  of,  136. 
Cerebrosulphatides,  185. 
Chemolysis,  Apparatus  for,  141. 
Cholesterin,  199. 

„        Reactions  of,  200. 

„        Isomers  of,  201. 
Cholophosphatides,  124. 
Cupric  inosite,  202. 
Cytophosphatides,  125. 

Formic  acid,  209. 

(Ilycerophosphoric  acid,  128,  9,  76. 
Glycoleucin,  221. 
(4rey  tissue,  231. 

Hematophosphatides,  124. 
Hypoxanthin,  192. 

Imides,  196. 
Inorganic  bases,  1 26. 
Inorganic  principles,  229. 
Inosite,  202,  198. 
Inosite  copper,  202. 
Isocholesterin,  201. 
Istarin,  120. 

Kephalic  acid,  73. 
Kephalin,  52. 

,,       Chemolysis  of,  72. 

„       Compounds  of,  61. 

„       Constitution  of,  89, 

„       Dialysis  of,  55. 

„       Preparation  of,  52. 

„       Reactions  of,  59. 
Solubility  of,  58. 
Kephaloidin,  67. 
Kephalophosphoric  acid,  73. 
Kerasin,  172. 

„      Chemolysis  of,  177. 

,,      Preparation  of,  172, 

,,      Reactions  of,  175. 

„     Solubility  of,  174. 
Krinosin,  191. 

Lactic  acid,  205. 
Lactophosphatides,  123. 
Last  oily  matter,  32. 
Lecithin,  42. 

„       Chemolysis  of,  49. 

„       Compounds  of,  46. 
Leucin,  196,  214, 
Leucin  copper,  217. 

Mercuramin,  259. 
Myelin,  94. 

.,      Compounds  of,  96. 

„      Preparation  of,  95. 

Needle  body,  184. 



Neuiin,  76. 
Neui-oplasiii,  1. 
Neuroplastin,  212. 
Neurostearic  acid,  169. 
Neurostearic  ether,  162,  109. 
Xitrogenised  fats,  188. 

Oleic  acid,  51. 
Oxigenised  principles,  199. 
Oxikephalin,  64. 
Oxikephaloidin,  70. 

Paracholesterin,  201, 
Paramyelin,  91,  44. 

„         Preparation  of,  93. 
Peroxikephalin,  66. 
Pettenkofer's  test,  156. 
Phosphatide.^  39. 
Phosphorised  principles,  39. 
Phrenosin,  138,  164. 

,,       Chemolysis  of,  141. 

„       Constitution  of,  168. 

„       Preparation  of,  138. 

„       Reactions  of,  167. 
Phytosterin,  201. 
Psychosin,  152,  154,  164,  170. 

„       Chemolysis  of,  155. 

Quantitative  relations,  231. 
Quantation  of  constituents  (of  entire 
brain),  252. 

Raspail's  reaction,  156. 

Specific  gravity  of  brain,  237. 
Spherocerebrin,  183. 
Sphingol,  116. 
Sphingomyelic  acid,  115. 
Sphingomyelin,  105. 

,,        Chemolysis  of,  115. 

,,        Compounds  of,  118. 

,,        Preparation  of,  108. 

„         Properties  of,  113. 
Sphingosin,  149,  169. 

„       Compounds  of,  150. 
Sphingostearic  acid,  116. 
Stearoconote,  23. 
Succinic  acid,  209. 
Sulphurised  principles,  ISO. 

Tyrosin,  196,  214,  216,  223. 

Water  of  colloidation,  2. 
White  brain  tissue,  234. 
White  matter,  30. 


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WITKOWSKI  (G.  J.)  Movable  Atlases  of  the  Human  Body   12 





Africa.  A  Contribution  to  the  Medical  History  of  our  West 
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2s.  6d. 

Alcohol,  in  some  Clinical  Aspects  :  A  Eemedy,  a  Poison.  By 
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Anaesthetics.  The  Dangers  of  Chloroform  and  the  Safety  and 
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Anatomy.  Aids  to  Anatomy.  By  George  Brown,  M.R.C.S.,  Gold 
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Examiner  in  Anatomy,  Royal  College  of  Surgeons,  and  Jas. 
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10       Bailliere,  Tindall,  and  Cox's  Books. 

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Bailliere,  Tindall,  and  Cox's  Books.  11 

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12      Bailliere,  Tindall,  and  Cox's  Books. 

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Bailliere,  Tindall,  and  Cox's  Books.  13 

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14       Bailliere,  Tindall,  and  Cox's  Books. 

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Bailliere,  Tindall,  and  Cox's  Books.  15 

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16       Bailliere,  Tindall,  and  Cox's  Books. 

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Cohnheim's  Pamphlet.  By  D.  H.  Cullimore,  M.K.Q.C.P., 
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Consulting  Physician  to  the  King  of  Burmah ;  Surgeon  H.M. 
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Bailliere,  Tindall,  and  Cox's  Books.  17 

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With  thirty-eight  engravings,  price  Is. 

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for  Diseases  of  the  Chest,  Lecturer  on  Materia  Medica  at 
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18       Bailliere,  Tindall,  and  Cox's  Books. 

Diphtheria.  Diphtheria,  its  Causes,  Pathology,  Diagnosis,  and 
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Students.  By  D.  J.  Cunningham,  M.D.,  Senior  Demonstrator 
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Domestic  Medicine.  Handbook  of  Popular  Medicine  for  family 
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Ear.  Text-book  of  the  Diseases  of  the  Ear  and  adjacent  Organs. 
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Etiquette.  A  few  Eules  of  Medical  Etiquette.  By  a  L.E.C.P. 
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ming, F.K.C.S.  Ed.,  and  H.  Aubeey  Husband,  M.B.,  F.E.C.S. 
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Bailliere,  Tindall,  and  Cox's  Books.  19 

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Eye.  A  Manual  of  Examination  of  the  Eyes.  By  Professor  C. 
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Eye.  The  Cure  of  Cataract  and  other  Eye  Affections.  By  Jabez 
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Fever.  On  the  Endemic  Heematuria  of  Hot  Climates,  caused  by 
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20       Bailliere,  Tindall,  and  Cox's  Books. 

Forensic  Medicine.  The  Student's  Handbook  of  Forensic  Medicine 
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Forensic  Medicine.    Aids  to  Forensic  Medicine  and  Toxicology.  I 
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Fractures.  A  Study  of  one  hundred  and  twenty-seven  cases  of 
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Geology.  Engineering  Geology.  By  the  same  Author.  Illustrated 
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Gynaecology.  A  Manual  of  the  Minor  Gynaecological  Operations 
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Gynaecology-  The  Diseases  of  Women  and  their  Treatment.  By 
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Hair.    The  Hair :  its  Growth,  Care,  Diseases,   and  Treatment ;  | 
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the  Assyrian  to  Modern  Times.    By  C.  H.  Leonard,  M.A., 
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Hay  Fever  ;  its  Causes,  Treatment,  and  Effective  Prevention  ;  Ex-  | 
perimental  Researches.    By  Chas.  Harrison  Blackley,  M.D. 
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terious disease." — Medical  Times. 

Hydrophobia.  The  Disease  as  it  appears  in  Man.  By  Horatio 
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Bailliere,  Tindall,  and  Cox's  Books.  21 

Heart.  On  Insufficiency  of  Aortic  Valves  in  Connection  with  Sudden 
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the  Royal  Free  Hospital.    Second  edition,  price  2s.  6d. 

Heart.  Contributions  to  Cardiac  Pathology.  By  the  same  Author. 
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Heart.  An  Essay  on  Fatty  Heart.  By  Henry  Kennedy,  A.B., 
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Histology.  Introduction  to  Practical  Histology.  By  George  Thin, 
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Hygiene.  Lessons  in  Military  Hygiene  and  Surgery,  from  the 
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Hygiene.  A  Manual  of  Sanitation ;  or,  First  Help  in  Sickness  and 
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Hygiene.  Healthy  Homes.  By  Stanley  Haynes,  M.D.,  M.E.C.S., 
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Hygiene.  Short  Lectures  on  Sanitary  Subjects.  By  ElCHARD  J. 
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Hygiene.  A  Manual  of  Naval  Hygiene,  with  Instructions  and 
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Hygiene.  Health  Aphorisms,  and  an  Essay  on  the  Struggle  for 
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Impotence.  On  Sexual  Impotence  in  the  Male.  By  William  A. 
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In  one  handsome  8vo.  volume  of  nearly  300  pages.  Cloth. 
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22       Bailliere,  Tindall,  and  Cox  s  Books. 

India.    Experiences  of  an  Army  Surgeon  in  India.    By  Surgeon-  j 
General  Gordon,  M.D.,  C.B.,  Hon.  Physician  to  the  Queen,  i 
A  Concise  Account  of  the  Treatment  of  Wounds,  Injuries,  and 
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Insanity.  The  Diagnosis,  Classification,  and  Treatment  of  Insanity  : 
A  Manual  for  Students  and  Practitioners  of  Medicine.  By  E.  C. 
Spitzka,  M.D.  President  of  the  New  York  Neurological 
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Illustrated,  cloth,  price  12s. 

"  Original  and  painstaking  as  everything  is  whicli  Professor  Spitzka  undertakes." — Medical 

International  Medical  Congress.  The  Commemorative  Portrait- 
Picture  of  the  International  Medical  Congress/ 1881.  By  Mr. 
Barraud.  This  Picture,  illustrating  the  most  memorable 
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executed  by  Mr.  Barraud,  contains  nearly  700  Likenesses  of 
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time  and  space  in  the  whole  history  of  Medicine." 

Kidneys.  Bright's  Disease  of  the  Kidneys.  By  Professor  J.  M. 
Charcot.  Translated  by  H.  B.  Millard,  M.D.,  A.M.  Ee- 
vised  by  the  Author,  with  coloured  plates,  price  7s.  6d. 

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Baillifere,  Tindall,  and  Cox's  Books.  23 

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26       Bailliere,  Tindall,  and  Cox's  Books. 

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Bailliere,  Tindall,  and  Cox's  Books.  27 

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Physiology.  A  Manual  of  Physiology.  By  E.  D.  Mapother, 
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28       Bailliere,  Tindall,  and  Cox's  Books. 

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Physiological  Laboratory.  Manual  for  the  Physiological  Labora- 
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Bradford,  lately  Medical  Officer  of  Health  for  the  Borough  of 

Bailliere,  Tindall,  and  Cox's  Books.  29 

Plant  Analysis.  Quantitative  and  Qualitative.  By  G.  Dragen- 
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Salt.  History  of  Salt,  with  Observations  on  its  Medicinal  and 
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Sanitary  Law.  A  Digest  of  the  Sanitary  Acts  of  England  and 
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Sewage.  The  Sewage  Question  :  Reports  upon  the  Principal 
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the  question,  and  to  apply  them  practically." 

Skin.  Diseases  of  the  Skin.  By  Sir  Erasmus  Wilson,  F.R.S., 
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ments of  the  Nervous  System.  By  T.  Stretch  Dowse,  M.D., 
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Robt.  Barnes, M.D.,  F.R.C.P.,  Obstetrics.  Laidlaw  Purves,  M.D.,  Aural  Surgery. 
Morell  Mackenzie,  M.D.,  The  Throat.  C.  S.  Tomes,  F.R.S.,  Dental  Surgery. 
F.  A.  Mahomed,  M.D. , The  Sphygmograph.    Sir  Erasmus  Wilson,  F.E.S.,  The  Skin. 

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30       Bailliere,  Tindall,  and  Cox's  Books 

Surgery.  Aids  to  Surgery.  By  George  Brown,  M.R.C.S. 
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Surgery.  The  Text-book  of  Operative  Surgery.  From  the  French 
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on  Surgery  at,  the  Royal  Infirmary,  Edinburgh.  *  Price  7s.  6d. 

Surgery.  A  Manual  of  the  Operations  of  Surgery,  for  the  use  of 
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Surgical  Anatomy.  The  Student's  Handbook  of  Surgical  Anatomy. 
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Bailliere,  Tindall,  and  Cox's  Books.  31 

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Therapeutics.     The  Principles  and  Methods   of  Therapeutics. 

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Throat.  Movable  Atlas  of  the  Throat,  and  the  Mechanism  of  Voice, 
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Throat.   Diseases  of  the  Throat.    By  Morell  Mackenzie,  M.D.  1 
(See  chapters  in  Gant's  "Surgery.") 

32       Bailliere,  Tindall,  and  Cox's  Books, 

Throat.  The  Throat  and  its  Diseases.  A  Practical  Guide  to  Diag- 
nosis and  Treatment.  With  100  typical  illustrations  in  chromo- 
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and  Ear  Hospital.    Second  edition.  Shortly. 

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ton  Jennings,  L.R.C.P.,  London,  M.R.C.S.,  formerly  House 
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Bailliere,  Tindall,  and  Cox's  Books.  33 

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Voice.  Artistic  Voice  in,  Speech  and  Song.  Dedicated  by  special 
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34       Bailliere,  Tindall,  and  Cox's  Books. 


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Bailliere,  Tindall,  and  Cox  s  Books.  35 

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36       Bailliere,  Tindall,  and  Cox's  Books. 





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Bailliere,  Tindall,  and  Cox's  Books.       37  | 

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